Blog posts

Interview with Professor Fiona Watt: ‘It is much better to try and fail than never to try at all’

Professor Fiona Watt is a leading British scientist in the field of Regenerative Medicine and the Executive chair of the MRC. She obtained her Bachelor of Arts and her Master’s Degree from the University of Cambridge and her PhD from the University of Oxford. After a two-year postdoc at the MIT, she came back to the UK to open her own lab at the Kennedy Institute of Rheumatology. Then, she moved to the Cancer Research UK, London Research Institute, and taught at the University of Cambridge, where she was also Deputy Director of the Wellcome Trust Centre for Stem Cell Research and of Cancer Research UK, Cambridge Research Institute. She then joined King’s College London, where she is currently directing the Centre for Stem Cells & Regenerative Medicine. Fellow of the Royal Society (since 2003), she has been the first woman president of the International Society of Stem Cell Research (2008).

 

Rebecca Womersley) What piece of advice would you have liked to receive at the beginning of your scientific career? 

That the people you meet early in your career are likely to pop up again for the rest of it.

 

Rebecca Womersley) Who are your role models, both within and outside of science, which have helped you ‘shaping’ your career? 

I would like to pay tribute to Brigid Hogan – she has not only been a great scientific role model but also a true friend and ally.

 

Elton Yeung) In 2008 you became the first woman President of the International Society of Stem Cell Research (ISSCR): have you ever experienced any significant challenges or setbacks in that role? 

No – the stem cell field has always attracted talented female researchers.

 

Matthew Brace) In 2018 you were appointed as the Executive Chair of the MRC: what attracted you to this role and what are your key goals for the coming years? 

The MRC is over 100 years old and yet its mission has remained constant – to improve human health through world-class research. Who wouldn’t want to lead such a wonderful organisation? I am very keen to support individual clinical and non-clinical scientists, to foster collaboration and translation, and to ensure that no-one is denied access to the infrastructure required to pursue their research.

 

Elton Yeung) Which specific traits of yours contributed to your success as a successful leader? 

Growing up, I only ever wanted to be a scientist. I’m adventurous and I tend to say ‘yes’ rather than ‘no’. And which skills and attributes are crucial for a successful leadership? I believe that it is important to listen to others, to have clarity of vision and to be compassionate.

 

Elton Yeung) How holding remarkable leadership roles have changed you as a human being? 

I have some sleepless nights and quite a few enemies.

 

Matthew Brace) How do you divide your time between the MRC and the Centre for Stem Cells and Regenerative Medicine at King’s College London, which you lead? 

I’m on secondment at the MRC for 80% of my time. That means I have one day a week at King’s and can hold weekly group meetings as well as catching up with everyone in my lab. I’m lucky that it only takes 25 minutes to walk between my office at the MRC and my lab. I can therefore fit lab time round MRC meetings and I don’t have to stick rigidly to one particular day of the week for King’s.

 

Matthew Brace) Stem cell research has advanced significantly over the past 20 years. What do you hope will be better understood in the next 20 years? 

I really hope that cell and gene therapies will continue to progress into clinical applications.

 

Rebecca Womersley) Many people assume there is a clearly defined boundary between arts and sciences: do you think so? Which role does creativity play in your work? 

I think scientists have much more in common – intellectually – with artists than with doctors, who are really craftsmen and women. Scientists need to have the time and space to be creative.

 

Elton Yeung) What would be your advice for women scientists who are about to start their journey in science? 

Go for it – it is much better to try and fail than never to try at all.

 

Matthew Brace) What is the most important advice you would give to a new PI on how to lead a lab?

Treat your team members with respect.

 

Rebecca Womersley) Looking backwards, which moment(s) are you particularly fond of and attached to? 

Over the years I have often taken my children to conferences. I will never forget my eldest telling me, after a conference reception, that I was ‘just a nerd magnet’.

Interview with Professor Marina Picciotto: ‘Positive feedback and mentorship are essential throughout a career’

 

Professor Marina Picciotto began her scientific career at Stanford University, where she received a B.S degree in biological sciences, and completed her PhD in Molecular Neurobiology at The Rockefeller University in New York City. She did a postdoc at the Pasteur Institute in Paris before joining Yale University in 1995, where she is currently the Charles B. G. Murphy Professor of Psychiatry and Professor in the Child Study Center. Among her many roles, she is also Deputy Chair for Basic Science Research within the Department of Psychiatry, Deputy Director of the Kavli Institute for Neuroscience and Editor-in-Chief of The Journal of Neuroscience. She won several prestigious awards, including the ‘Presidential Early Career Award for Scientists and Engineers’ (2000), the election to the National Academy of Medicine (2012) and as AAAS (American Association for the Advancement of Science) Fellow (2014), and the ‘Bernice Grafstein Award for Outstanding Mentorship’ from the Society for Neuroscience two weeks ago.

Does received a bachelor’s degree in Biology from the University of Sussex and is currently a MSc student in Translational Neuroscience at Imperial College London. The ever-changing world of science fascinates her, especially when it comes down to understanding the complexity of the human brain. To quote Francis Crick: ‘There is no scientific study more vital to man than the study of his own brain. Our entire view of the universe depends on it’.

Have you always known you wanted to do a PhD or was it something you decided as a Master student?

When I was an undergraduate, I worked in a laboratory, but thought I wanted to do a medical degree. By the end of my university degree, I knew I didn’t want to leave the lab, but only applied for graduate school after realizing late that I didn’t want to go to medical school or practice medicine. My graduate program did not offer a Masters degree.

Have you ever had to deal with the ‘imposter syndrome’, especially during the early stages of your career? 

I only started to have “imposter syndrome” once I got a faculty position. I always had doubts during training that my project would work out well or that I would be able to complete the experiments, but I was sure I was absolutely right to be there. When I became an assistant professor, I had many more doubts about whether I would be able to do what was needed to maintain a research program and continue to find out new things while supporting the work. While the doubts and anxiety about my abilities definitely got better as I became more senior, the internal dialogue about whether I should be doing what I’m doing and whether I have the abilities to do it is always there.

What would be your advice to neutralise the ‘imposter syndrome’?

I think most of us struggle with this and it is not something that should make us stop working as scientists if we continue to enjoy the work. I tell the internal voice that I will stop only when I decide it isn’t worth it to me or until someone actually makes me go home.

You have worked on nicotine and addiction. What is your stance on the use of e-cigarettes to help curb smoking addictions?

Anything that helps current smokers stop smoking is a huge public health boon. E-cigarettes are less harmful to addicted smokers than burned tobacco products. That said, the tobacco companies have taken advantage of this to market e-cigarettes to adolescents and non-tobacco users as perfectly safe. That is not true and neglects the fact that e-liquids contain a large number of chemicals that are being taken into the lungs, even though they aren’t “burned” and there is a large literature on the effects of nicotine on the developing brain. I don’t believe pregnant women or teenagers should vape nicotine.

Among the many roles you have, you are the editor-in-chief of The Journal of Neuroscience, Professor of Psychiatry at Yale University, PI of the Picciotto Lab and Deputy Director of the Kavli Institute for Neuroscience. How do you reconcile all these roles?

In some ways the roles are complementary. For example, I learn a tremendous amount about current neuroscience from my work at the Journal of Neuroscience and that improves the work in my own lab. I also get a lot of satisfaction from helping junior faculty succeed in their own work, my main role as Deputy Chair of the Department of Psychiatry, and that is a satisfaction that keeps me going in my academic career. Sometimes all the roles require my attention in a burst and it is challenging, but for the most part I am able to handle them by having people who help with many of the details and by learning what is most important for me to pay attention to, what is easy to get off my desk quickly, and how to delegate when I am not the right person to do something.

How do you achieve a good work/life balance?

Balance is probably a bad term that we have all adopted. What I think we should strive for is an understanding of our own values and needs that allow us to understand what we are willing to devote to each part of our lives. I have a pretty strict hierarchy of what is important to me, so my desire to be with my daughter and family on most evenings and weekends and also take care of them when they needed me most, allowed me to prioritize my time in a way that, for the most part, worked for me. My work is very important to me, so there is a baseline time commitment that I was also not willing to give up. My “balance” is almost certainly not the same as someone else’s. Determining what your own values are is essential to being able to find a work arrangement that is coherent with those values, and to spend the time with family that works with a partner or other family members.

What are your main tasks as editor-in-chief of The Journal of Neuroscience?

I have served in each of the editorial roles at The Journal of Neuroscience during my career, starting as an Associate Editor, then Reviewing and Senior Editor, and each has different demands. At The Journal of Neuroscience, Associate Editors are called on to serve as third reviewer and to step in when another reviewer is very late or disappears. Reviewing Editors invite reviewers and make the first decision on a manuscript they handle. Senior Editors make the final decision and calibrate the decisions across multiple Reviewing Editors. As a result, the Editor in Chief does not handle manuscript review personally. I will be called in if there is a difficult appeal or if there is any consideration of scientific or ethical misconduct. I also get to select the new editors when there is an opening on the editorial board, set Journal policies, write editorials to publicize our policies and communicate about best practices in experimental design or other issues important to the field, work with our Features Editor to select articles to highlight each week, communicate with Reviewing and Senior Editors to coordinate our editorial policies and decisions, work with our publisher (the Society for Neuroscience) to make sure that the Journal is operating appropriately, and most fun, work with our Features Editor and administrative staff to select the cover each week.

Pre-registration is something relatively new which some academic journals are starting to accept. How do you think this will affect the world of scientific research and publishing? 

Pre-registration is ideal for some types of studies where the experimental design is already clear. I think it will increase the reporting of negative findings, improve the power of pre-registered studies and overall increase the rigor of studies for which all the experiments can be predicted in advance. Pre-registration will not work for all types of studies, however. There are many things that are explored in basic science labs that cannot be predicted, and much of the work to come up with a new direction in this type of “discovery science” cannot be predicted. Science needs rigor, but it also needs unpredictability and exploration. Both need to co-exist and the limitations of each approach should be accepted. In the end, I believe that science relies most on replication and building on what was discovered. If a result is robust, it will be used by the next scientist to move the field forward. If not, it will ultimately be abandoned. There are ways to make sure that dead ends are abandoned more quickly, but we cannot avoid them completely.

How would you further support women in STEM within academia, in order to increase their presence?

Women are discouraged from STEM positions in academia at different points of their education and careers. In some fields such as mathematics, women face barriers early in their education when their abilities are still doubted by educators and maybe even family and other students. The public awareness campaigns that are currently encouraging entry into STEM fields can help with that, and teacher training, elimination of “weed out” courses for math and engineering, and changes in the format of early teaching may help in those fields. In other STEM fields, like biological sciences, there are equal numbers of students who enter, but the loss becomes greater at each stage of career development. At the postdoc level, we have to acknowledge that a handful of the most “prestigious” labs are often the source of candidates for subsequent academic positions. If funders of those large labs require equity in the trainees in those labs and if university search committees broaden their search beyond trainees from those labs, there will be a larger pool of diverse junior faculty members. At later stages of academic careers, our internal representation of what a “smart” person looks like and what a “leader” looks like also plays a very important role in who we select as chairs and deans. These types of unconscious biases are held by all of us, and the more that these biases can become acknowledged, the more we can broaden what we think a “leader” looks like, the more different types of leaders we will select. Finally, many individuals get discouraged after years of trying to change a system in which they feel they are either slighted or not recognized. An understanding that positive feedback and mentorship is essential throughout a career, not just during training, may help keep talented scientists in academic careers by making them understand that they are valued despite the obstacles or setbacks they continue to encounter.

Which changes would you like to see in the scientific landscape within the next 5-10 years?

I would like to see scientists continue their move to collaborate across disciplines and find ways to learn from others in fields as distant as possible from their own, both across scientific disciplines and between science and arts or other humanities. I would like to see a continued move by funding agencies to put aside a portion of their grants to very risky projects that may not work out and to find a way to communicate results of “failed” studies, rather than letting them disappear. Finally, as a neuroscientist, I hope to see a continued focus on integrating results across levels of observation (molecular, cellular, circuits, systems, behaviors, organisms) so that we can embrace the complexity of nervous systems and how they allow all of us with neurons to interact appropriately with our environments.

Interview with Dr Magdalena Sastre: ‘Inspired by Marie Curie and Santiago Ramón y Cajal’

Dr Magdalena Sastre is Reader in Molecular Neuroscience at Imperial College London. She graduated in Sciences and did her PhD in Biology and Health Sciences at the University of the Balearic Islands, Spain. She trained in Neuroscience in the USA (Cornell University and New York University) and in Germany (Universities of Munich, Bonn and Frankfurt). She is interested in the molecular mechanisms whereby inflammation impacts on aging-related neuronal degeneration. Her research is based on a multidisciplinary approach using molecular/cell biology, pharmacological, imaging and biochemical techniques.

Catriona completed her undergraduate degree in Neuroscience at the University of Glasgow where she investigated the auto-immune disease Guillain-Barré syndrome. Throughout her MRes in Experimental Neuroscience at Imperial College London, she has since moved towards a computational neuroscience approach, from her first project focussing on cell death in Multiple Sclerosis, to her subsequent projects in attentional control in Huntington’s disease and metastable cognitive states in Autism spectrum disorder.

What drew you to scientific research?

During my Biology degree we were allowed to work in labs during our free time and I ran small projects in different fields; I did a small project on Botanics, another on Limnology, which is the study of inland aquatic ecosystems,and did my masters on the Physiology of obesity. However, my interest in Neuroscience grew during the last year of my degree, when I learnt that mental disorders have a biological basis; this was a big driver for my PhD, which was on the role of noradrenergic signalling in the brain of suicide victims and I found this research very exciting.

Your research is focused on molecular and cellular aspects of neurodegeneration: what is your favourite aspect of a job in research?

There are many aspects that I like, starting by designing a project (a new idea), performing the experiments, teaching future researchers, attending conferences, meeting new people and publishing the results, so reaching the research community around the World. I have met so many interesting people thanks to science that are now my friends, it is great to still get in touch with those colleagues!

What is the most exciting research currently going on in your area of research, both within and outside of your lab?

In the last few years, the interest for the role on Neuroinflammation in the field of neurodegeneration, and in particular Alzheimer’s disease (AD), has grown significantly. We have been working in this area for many years. In particular, now we have several papers in preparation, analysing the role of astrocytes in Alzheimer’s disease, using different approaches from animal models to potential therapies in humans.

In your opinion, how important is the public awareness and education of scientific advances in a world where misinformation can spread uncontrollably? 

It is really important. I think that public engagement activities are essential to educate people and to help understanding our work. Unfortunately, a lot of information in the internet and newspapers are “fake news” and they spread very quickly.

What role can scientific researchers play in the stimulation and moderation of accurate and meaningful discussion between the science community and the public?

As I said above, it is important to give talks to the general public and to students, participate in documentaries, open the labs (we do that once a year) and other types of activities. We always receive very good feedback from the public attending our events and they then become more aware on how they can also contribute to science, by for instance, donating their brains for research (when they die, of course)!

Have you observed a positive change in the employment of women in more senior roles in academic research in the recent years?

Unfortunately, I haven’t seen a big change. The percentage of women in senior roles at the university is quite low. We are not taken very seriously and often are offered positions in teaching roles and responsibilities rather than research, although most of the PhD student and postdocs in our department are women.

Donna Strickland, the third female to earn the Nobel Prize in Physics (2018) said that she was surprised by the focus on her gender, and that she sees herself as a scientist, rather than a woman in science. Do you believe the emphasis on gender in media coverage of scientific accolades is beneficial in the quest for equality across STEM subjects?

It is clear that women need more support, because there is undoubtedly a bias regarding prizes and reaching senior positions in Academia. I do not want that women are offered positions based on a certain number, but I believe that there are great women scientists that have been obviated and forgotten. In part it is our fault, because we tend to be more humbled than men are.

Do you have anyone who is particularly inspiring for you? Within or outside of science?

One of the most inspiring scientists for me has been Marie Curie, for her dedication. Another great scientist that I admire is Santiago Ramón y Cajal, the funder of modern Neuroscience. Science is not only great ideas, but hard work!

In what direction do you hope to take your lab over the next few years?

We will continue exploring the role of Neuroinflammation in Alzheimer’s disease, trying also to find potential new treatments for this devastating disease.

If you had to pick any other research area to study, what would it be?

It would have to be in the field of arts and history.

A brief reflection on (neuro)science and social responsibility

Alexandra did her undergraduate in Molecular Biotechnology at the Technical University of Munich and worked on a project related to familial ALS during the MSc in Translational Neuroscience at Imperial College London. She has started her PhD at the Max-Planck-Institute of Neurobiology in Munich.

‘What was once thought can never be unthought’is one of the most famous quotes from ‘The Physicists’ written by Friedrich Dürrenmatt. Published in 1963, it treatises the responsibility of science. Even though its historical background is the Cold War, the topic of science responsibility towards society is still extremely relevant nowadays. At the crossroads between science and society, the word ‘responsibility’includes a plethora of different aspects, from the application of scientific findings to the correctness and the reproducibility of scientific research, and beyond. Here we will briefly discuss the case of neuroimaging in a legal context, reproducibility and prevention of misconduct.

When neuroimaging enters the court

Neuroimaging findings have been recently used for dangerousness assessments in criminal trials as part of the psychiatric testimony (Gkotsi and Gasser, 2016). Neuroimaging is a term that includes different methods to visualise the structure of the brain or its responses to tasks. A widely used imaging neuroimaging technique is fMRI, which relates neuronal activity, either within a task or a resting state, to neuronal networks by measuring the change in oxygen in the blood. These changes (known as BOLD, an acronym for blood oxygen dependent contrast) are supposed to reflect changes in neuronal activity in the areas they occur.

However, fMRI still has some limitations. One of them is its limited temporal resolution (Ugurbil, 2016). Another one is linked to the fact that the measurement of neuronal activity is indirect, as it relies on changes in the blood supply of certain areas. For this reason, imaging data should be used very carefully, especially since, at first glance, they might look like ‘objective criteria’ to determine a person’s dangerousness (Gkotsi and Gasser, 2016). As easy explanations are tempting in times with rising public fears, Gkotsi and Gasserwarn about an ‘instrumentalisation of neuroscience in the interest of public safety’.

In addition to this, trying to relate features of dangerousness, like violence, to a single biological cause is a ‘simplistic falsity’ as it negotiates the social influences on an individual (Pustilnik, 2008). On top of that, the legal and social definition of what is seen as a violent behavior itself changed over time, making explanations of dangerousness even more complex. With our brains being extremely interconnected, it is not possible to relate something which is as complicated on different levels as violence only to a single brain region (Pustilnik, 2008). Even if certain brain regions like the prefrontal cortex, which is the anterior part of the brain, relate to ‘social control’, they are also linked to ‘problem solving’ or ‘pain processing’,and they are always integrated in a wider network (Onget al., 2018). Moreover, functional-anatomical correlations does not inform us about causality (Pustilnik, 2008).

Furthermore, this would also lead to the danger of stigmatisation of people with neurological or psychiatric disorders (Gkotsi and Gasser, 2016). For example, schizophrenia could be related to an ‘absence/diminishment of criminal responsibility’ in a systematic review (Tsimplouliset al., 2018). However, the same review states that ‘many individuals with schizophrenia do not meet the legal criteria for an insanity plea’. This serves as a reminder for a careful approach to every individual case since a psychiatric condition per seis not a factor for committing. Stigmatisation has negative effects: a large-scale study showed that, independently from the symptoms, only the diagnosis of schizophrenia lead to the diagnosed person being described as more ‘aggressive’, ‘dangerous’and less ‘trustworthy’(Imhoff, 2016). Moreover, the diagnosis of a risk of developing schizophrenia was related to stigmatisation, although more information about the actual risk of developing the psychosis could reduce the stigma (Yanget al., 2013).

Reproducibility and prevention of misconduct

Science needs to be reliable and reproducible. In 2016, a Naturesurvey conducted among more than 1500 researchers showed that more than 70% of them were unable to reproduce their own or another person’s findings (Baker, 2016). This does not necessarily mean that science is facing a crisis (Fanelli, 2018), keeping in mind that reproducibility issues can help to develop the state of knowledge by detecting hidden variables (Redishet al., 2018). Still several researchers appeal to take actions to ensure responsibility when possible. Those include publishing of methods in more detail as well as publishing negative results in conditions not used for the final experiment that gave the expected results, as this would also help other scientists (Drucker, 2016). Another suggestion would be to introduce a‘reproducibility index’for senior researchers as an easy way to show how many of their findings have been reproduced by another group (Drucker, 2016). Moreover, other scientists suggested that it should be easier to publish retractions while distinguishing between scientific misconduct and the recognition of being wrong due to later experiments (Flier, 2017). It was also pointed out that the peer-reviewing process should be publicly available for the benefit of  the whole community as other scientists could potentially profit from the suggestions made within this process (Flier, 2017). In addition, work of reviewers would be acknowledged while professional conflicts would be made obvious. During this process, it should be made sure that strict reviewers are not made target of harassment of disappointed authors(Flier, 2017).

To maintain responsible science, prevention of misconduct is another essential aspect. Another Naturesurvey conducted on more than 3,200 scientists found out that ‘slightly more than half of non-PIs said they had often or occasionally felt pressured to produce a particular result in the past year’(van Noorden, 2018), and‘Group and authority pressure’was one of the pitfalls named for research misconduct (Gunsalus and Robinson, 2018). More training was advocate to sensibilise young scientist on the theme of research misconduct and assessing the research climate in the lab as a further possible tools preventing this issue (Gunsalus and Robinson, 2018).

Conclusions

Overall, raising awareness of these problems in scientific research is the first step towards a more responsible scientific and social environment. Together with the suggestions made by different scientific groups, including more scientific training and critical reflection of their own research, everyone can contribute to this goal.

In ‘21 points to the Physicists’, Dürrenmatt stated that ‘the content of physics is the concern of physicists, its effect the concern of all men.’ As this is not only true for physics but for scientific research as a whole, responsibility should be a key characteristic of science.

 

 

References

Baker, M (2016): 1,500 scientists lift the lid on reproducibility. Nature 533 (7604), 452–454.

Drucker, DJ (2016): Never Waste a Good Crisis. Confronting Reproducibility in Translational Research. Cell metabolism 24 (3), 348–360.

Dürrenmatt, F (1963): The physicists. A play in 2 acts.

Fanelli, D (2018): Opinion. Is science really facing a reproducibility crisis, and do we need it to? Proceedings of the National Academy of Sciences of the United States of America 115 (11), 2628–2631.

Flier, JS (2017): Irreproducibility of published bioscience research. Diagnosis, pathogenesis and therapy. Molecular metabolism 6 (1), 2–9.

Gkotsi, GM; Gasser, J (2016): Neuroscience in forensic psychiatry. From responsibility to dangerousness. Ethical and legal implications of using neuroscience for dangerousness assessments. International journal of law and psychiatry 46, 58–67.

Gunsalus, CK; Robinson, AD (2018): Nine pitfalls of research misconduct. Nature 557 (7705), 297–299.

Imhoff, R (2016): Zeroing in on the Effect of the Schizophrenia Label on Stigmatizing Attitudes. A Large-scale Study. Schizophrenia bulletin 42 (2), 456–463.

Ong, W-Y; Stohler, CS; Herr, DR (2018): Role of the Prefrontal Cortex in Pain Processing. Molecular neurobiology.

Pustilnik, AC (2008): Violence on the brain: a critique of neuroscience in criminal law. Harvard Law School Faculty Scholarship Series.Paper 14

Redish, AD; Kummerfeld, E; Morris, RL; Love, AC (2018): Opinion. Reproducibility failures are essential to scientific inquiry. Proceedings of the National Academy of Sciences of the United States of America 115 (20), 5042–5046.

Tsimploulis, G; Niveau, G; Eytan, A; Giannakopoulos, P; Sentissi, O (2018): Schizophrenia and Criminal Responsibility. A Systematic Review. The Journal of nervous and mental disease 206 (5), 370–377.

Ugurbil, K (2016): What is feasible with imaging human brain function and connectivity using functional magnetic resonance imaging. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 371 (1705).

van Noorden, R (2018): Some hard numbers on science’s leadership problems. Nature 557 (7705), 294–296.

Yang, LH; Anglin, DM; Wonpat-Borja, AJ; Opler, MG; Greenspoon, M; Corcoran, CM (2013): Public stigma associated with psychosis risk syndrome in a college population. Implications for peer intervention. Psychiatric services (Washington, D.C.) 64 (3), 284–288.

 

Picture credits: Wellcome Collection (picture by Gabriel González-Escamilla)

The HIV-positive Brain in the ART Age

Ines has completed a research project in computational neuroscience, focusing on learning impairments in Parkinson’s disease. Her previous research experience during her BSc included studies on rodent models of ADHD (University of Manchester) and Alzheimer’s disease (Institute for Functional Genomics, Montpellier, France). Her interest in writing about HIV stems from the fact that she was born and grew up in Mozambique, a country where HIV/AIDS continues to be a significant health threat, affecting over 10% of the population and where over 800,000 people live with HIV on ART.

On the 5th of June 1981, the cases of 5 patients infected with what would later come to be known as the human immunodeficiency virus (HIV) were reported for the first time in Los Angeles, USA (CDC, 1981). In the years that followed, the virus rapidly spread across the globe, with a peak of new infections (3.5 million) recorded in 1997 (Roser and Ritchie, 2018). By 2016, there were approximately 36.7 million people living with HIV worldwide (UNAIDS, 2017).

The human immunodeficiency virus is transmitted through contact with bodily fluids. Although sexual transmission is the most common form, HIV can also be passed on through contact with infected blood or by vertical transmission. The latter refers to the case of mothers transmitting the virus to their children during pregnancy, childbirth or breastfeeding (Levy, 1993; Roser and Ritchie, 2018).

HIV belongs to a subgroup of viruses called lentiviruses. The term lentivirus comes from the Latin lentus, which means slow, owing to its long incubation period in the infected organism before any overt manifestation of disease is detectable (Haase,1986). Due to this defining characteristic, HIV infection is initially asymptomatic, but if left untreated, it may have notable negative effects and eventually lead to death (Moir et al., 2011). Although the viral infection in itself is not usually the direct cause of death, HIV suppresses the immune system, making patients particularly vulnerable to certain cancers and other infections, while being unable to naturally fight them. This state of immunosuppression and the spectrum of potentially fatal symptoms that accompany it are collectively termed Acquired Immune Deficiency Syndrome (AIDS) (Levy, 1993; Weiss, 1993; Naif, 2013). Over 70% of HIV infection cases have been reported in sub-Saharan Africa, where, to date, AIDS ranks as one of the major causes of death among adults (Roser and Ritchie, 2018).

Where the virus meets the brain

There is currently no vaccine or cure for HIV infection. Nonetheless, the last 37 years have seen major advances in the understanding of its pathophysiology as well as the wide range of clinical manifestations it may have. Among them, several neurological complications have been identified (Saloner and Cysique, 2017, Grant et al., 1987). These complications can be broadly categorised into two classes: primary and secondary. Primary complications arise as a direct effect of HIV replication in central nervous system cells; the most notable example being HIV-associated neurocognitive disorder (HAND). Secondary complications, however, result from the previously mentioned opportunistic infections that occur when patients are immunosuppressed (Kolson, 2017).

Evidence suggests that HIV enters the central nervous system within the first few weeks post-infection, an early stage in the course of the disease (Abidin et al., 2018). As the virus replicates, it may trigger a cascade of events at the molecular level that lead to chronic inflammation in the brain (Kolson, 2017). Consequently, the central nervous system may undergo primary damage that is only detected much later, when patients present with neuropsychological symptoms (Ellis et al., 2007, Abidin et al., 2018).

One of the most severe forms of cognitive impairment observed among patients is HIV-associated dementia (HAD) (Saylor et al., 2016, Grant et al., 1987, Ellis et al., 1997). In the early years of the AIDS epidemic, this was a common feature of a patient’s clinical presentation and was often fatal. This would go on to be so until the development of antiretroviral drugs in the mid 1990s (Saylor et al., 2016).

The impact of ART

Since the introduction of antiretroviral therapy (ART), there has been a major shift in  prognoses for patients living with HIV as well as in the manifestation of the virus in the brain. Briefly, antiretroviral drugs are a group of pharmacological agents that target different parts of the HIV life cycle. ART is not capable of eradicating the virus, but it is able to inhibit its replication, thus, reducing or entirely preventing immunosuppression (Ellis et al., 2007). In the present day, an HIV-positive diagnosis in areas where ART is readily available no longer necessarily translates to an imminent death or even to the development of AIDS (McArthur et al., 2003). Instead, HIV infection can become a chronic condition that allows patients to have close to normal life expectancies, especially when treatment is started early (Wandeler et al., 2016, Saylor et al., 2016). With regard to the brain, in patient populations undergoing ART, the incidence of severe neurocognitive problems such as HAD and that of secondary neurological complications has been shown to decrease drastically (Saylor et al., 2016).

Nevertheless, there are limitations to the therapeutic effect of ART. A neurologically relevant example of this is the finding that the blood brain barrier (BBB) restricts the entry of certain antiretroviral drugs into the central nervous system (Langford et al., 2006). The blood brain barrier separates neurons from circulating blood. Its permeability is highly selective, allowing for tight control of the material that is exchanged across it (Zlokovic, 2008). However, it has been hypothesized that by hindering the penetrance of certain antiretroviral drugs, the BBB allows the activity of HIV to partially persist in the brain (Ellis et al., 2007). In accordance with this hypothesis, over 50% of the HIV-positive population is estimated to be susceptible to HIV-associated neurocognitive disorders; though these are often milder forms of HAND than those observed pre-ART (Abidin et al., 2018, Chakradhar, 2018). However, it can also be hypothesised that independent of ART penetrance, such cognitive problems may be long-term sequelae of primary insults (Ellis et al., 2007).

Furthermore, the consequences of long-term administration of ART are currently not fully understood and it has been suggested that it could also play a role in neuronal damage (Kolson, 2017). Nevertheless, whatever the exact causes may be, mild forms of HAND are undeniably common among patients and can be detrimental to their quality of life (Saylor et al., 2016; Abidin et al., 2018). With the expanding availability of ART, the importance of addressing such issues has gained increased recognition given that  HIV positivity has become a long-term status for many of those affected (Wing, 2016; Chakradhar, 2018).

The aftermath of survival: from development to ageing 

The fact that ART allows HIV-positive individuals to live much longer than they could in the beginning of the AIDS epidemic has set several new neuroscience research challenges as there are still many gaps in the understanding of the long-term effects of HIV infection (Wing, 2016).

On one end of the age spectrum, there are increasing survival rates among children and adolescents who initiated ART soon after vertical transmission, creating a window of opportunity to investigate the role of HIV infection in the developing brain (Li et al., 2018, de Martino et al., 2000). Further, this group constitutes a new population of individuals, many of whom are now adults, who have been on ART for their entire lives.

On the other end, with the continuous (though decreasing) occurrence of new HIV infections and a reduction in deaths due to AIDS (UNAIDS, 2017), there is a growing HIV-positive population that is ageing (Wing, 2016). In fact, a study based on people living with HIV in the Netherlands projected that by 2030, almost 75% of this population would be composed of people aged 50 or older (Smit et al., 2015). This raises interest in the interaction between HIV infection and ageing-associated neurocognitive processes.

In 2016, Turner and colleagues reported the first case of an individual with both HIV and Alzheimer’s disease, the most common cause of dementia (Turner et al, 2016). As more and more of these cases appear, it is important to find the means to distinguish between Alzheimer’s and HAND symptoms as well as to identify any links that may exist between them (Chakradhar, 2018). In recent years, it has often been debated whether HIV infection might accelerate ageing (Chakradhar, 2018, Deeks et al., 2013). Given, that age is the strongest risk factor for Alzheimer’s disease, this could be a potential link to HIV. Furthermore, a study in neurons derived from mice found that ART may contribute to the deposition of the protein, amyloid beta, a hallmark of Alzheimer’s disease pathology (Giunta et al., 2011). Taken together, these ideas build a case for the possibility of interactions between age, HIV and ART.

Future prospects: where to look for clues?  

One of the main aims for the future of neuro-HIV research is to find differences, be they anatomical, functional or molecular, between healthy and HIV-positive individuals that might help detect and/or predict the occurrence of neurological problems at early stages (Clifford, 2017). Such characteristic traits of pathological processes are known as biomarkers. The use of tools to visualise the brain in vivo (neuroimaging) has been an increasingly popular approach to solving this problem. For example, a few recent studies have applied neuroimaging techniques to the investigation of anatomical and functional changes in the brains of young people infected with HIV (Ackermann et al., 2016, Randall et al., 2017, Toich et al., 2017). Others have looked into characteristics that may distinguish the effects of the virus from processes associated to ageing or non-HIV-related neurodegeneration (Zhang et al., 2016, Cole et al., 2017). Further, a study by Wiesman et al,. (2018) specifically investigated potential imaging-based biomarkers of HAND. These studies have highlighted specific alterations in grey matter volume, white matter integrity and network connectivity. In time, such findings may begin to shape an HIV-specific neurocognitive profile. Ideally, this will improve prognosis for patients and help define new therapeutic approaches that might improve the quality of life of those living with HIV.

 

 

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Ackermann C, Andronikou S, Saleh MG, Laughton B, Alhamud AA, van der Kouwe A, Kidd M, Cotton MF and Meintjes EM (2016) Early antiretroviral therapy in HIV-infected children is associated with diffuse white matter structural abnormality and corpus callosum sparing. American Journal of Neuroradiology 37(12):2363-9.

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Interview with Professor Anne Lingford-Hughes: Neuroscience, Psychiatry and Passion

Professor Anne Lingford-Hughes is the Head, Centre for Psychiatry and Professor of Addiction Biology at Imperial College London. She is also a Consultant Psychiatrist with a particular interest in pharmacological treatments of alcohol problems and other substance addictions at Central North West London NHS Foundation Trust. Her research has focused on using neuroimaging and neuropharmacological challenges to characterize the neurobiology of addiction

The key aims of this new blog are to enhance the curriculum and innovate pedagogy, highlight the contribution of women in academia within and outside the College, and engage and inspire the society. The founder and editor of the blog is Dr Stefano Sandrone, Teaching Fellow within the Faculty of Medicine, and the contributors are Imperial’s MSc Translational Neuroscience students.

Swetha Umashankar) What inspired you to choose scientific research as a career? 

At school I liked all science subjects but particularly biology and chemistry. I also liked doing projects since you were allowed to do subjects in more depth. Projects also helped to satisfy my curiosity about things that I could not find the answer to!  There are no scientists in my family so my teachers at school and my tutor at University were very important in helping me develop my career.

Lucía Luengo Gutierrez) What were the difficulties you have to deal with when you decided to start a science career? 

I do not really remember any particular difficulties. It was helpful being able to move within the UK and to the USA for my post-doc since I had no particular ties to one place. I saw for some colleagues that it was much harder to take up opportunities since they had family and financial responsibilities.

Swetha Umashankar) How would you describe your career trajectory so far?

Hard one! I think most people think they can always do better or differently? You can always find people you regarded as contemporaries at the start of your career who have done better or worse than you. On the whole I am happy with where I am and what I want to do next.

Caroline Schaufelberger) Was there a specific event or reason that aimed your interests in research towards addiction?

The lab I joined for my post-doc was studying the GABA-A receptor. Amongst a range of modulators that we studied, it was known that some of the effects of alcohol were mediated through this receptor. When I returned to research after completing my clinical training I joined a group whose primary focus was on schizophrenia. At that time evidence had been growing for a potential role for the GABA-A receptor in schizophrenia. Having failed to get a fellowship to support an imaging study of the GABA-A receptor in schizophrenia, I reapplied to study alcoholism – and got funded. At that time very few people were looking at the biology of alcoholism using brain imaging so it was quite novel.

Claudia Ghezzou) Throughout you career, what have been the motivations and incentives that have kept you focused in your impact as a researcher regardless of the possible difficulty of the processes or discouraging results from the research carried out?

Being in the clinic where there is obvious unmet need continues to motivate me to keep going – particular as addicts are a vulnerable, stigmatised and often marginalised within society.  Being a member of a good team who can celebrate and commiserate is crucial. Support and understanding from my family has also been crucial.

Pavlina Pavlidi) Did you experience any conflicts between your career and personal life choices?

All the time! It is a constant juggling act particularly as for the last 10yrs I have lived away from my family during the week so I try to limit activities which impact on time with them at weekends. Modern technology has been helpful – so even if I am not at the dinner table with them in person, I can join via skype. On the other side, they have had some amazing experiences when they have joined me on a ‘work trip’ so they have benefited as well.

Shinil Raina) What gaps do you think exist between neurobiological and clinical research in the field of addiction?

Gaps still exist though having to argue that there is a neurobiology to addiction is less of an issue now compared with 20yrs ago. Compared with other areas of psychiatry we know quite a bit about the brain in addiction and many of the medications used came from knowledge about pharmacology and neurobiology. I think many people are aware of this however most people who work in the addiction field have no training in this area. This then means that the number of clinical researchers in this area is limited – this needs to change if we are to improve prevention and treatment. So to me the gap is about lack of people trained in research and who work clinically rather than highlighting a gap in a particular area.

Caroline Schaufelberger) To what extent do you think that the research you are doing in addiction will have an impact on the societal understanding of addiction?

I hope that by people understanding the role of the brain that addiction is destigmatised, that it is no longer seen as due to someone ‘lacking moral fibre’.

Ryan Dowsell) What’s the most ridiculous scientific report you’ve seen in the media?

Another hard question! No one report comes to mind but I do find it intriguing how the media can report that ‘alcohol is bad for you’ and ‘alcohol is good for you’ without any sense that they are being inconsistent or informing the reader how to interpret research.

Shinil Raina) Why do you think in the current political climate are some politicians against the advancements in science?

I am not sure it is just current – it has always been this way. I am not sure they are against scientific advances as such but more about how much they will cost financially and whether it will be popular with voters. As one elected official was quoted as saying when asked about cuts to budget for addiction services – no ‘man on the street’ in the run up to an election has ever asked me to give more money to addicts. Another factor is that in the UK (I do not know about elsewhere) very few politicians are scientists and also they like yes/no – whereas we speak in terms of probability.

Jessica Hain) Are there any areas in addiction research which you would like to see explored in the future?

I think we need more in the area of opiate addiction where we have not really seen a step-change in what we can offer for decades – we need new treatments to help those struggling with street heroin and also those whose use of opioid analgesics have escalated uncontrollably.

Leire Melgosa) What is your advice to young scientist (i.e. a hard truth or something we tend to worry about but we should not)?

Jessica Hain) Do you have any advice for neuroscience students?

Same answer to both – if you are interested in a topic or technique, join a group working in this area and use it like an apprenticeship. I think it is also important to have people around you that you enjoy working with to mentor and help you to keep going towards your goal. Neuroscience is a great area to be in and there is always something new and exciting happening.

Interview with Professor Helga Nowotny: ‘In basic or fundamental research one does not know what one will find, yet it is precisely this uncertainty that is attractive’

 

Professor Helga Nowotny is Former President of the ERC, the European Research Council and one of its Founding Members. She is Professor emerita of Science and Technology Studies, ETH Zurich and Nanyang Technological University Visiting Professor (source: http://helga-nowotny.eu/).

The key aims of this new blog are to enhance the curriculum and innovate pedagogy, highlight the contribution of women in academia within and outside the College, and engage and inspire the society. The founder and editor of the blog is Dr Stefano Sandrone, Teaching Fellow within the Faculty of Medicine, and the contributors are Imperial’s MSc Translational Neuroscience students.

Kausar Raheel) You hold different positions throughout your career. What is the most rewarding aspect of your job? What drives you?

Being able to follow what I like to do: to be curious about the world, people, ideas…and passionate in exploring how we might improve the human condition.

Kausar Raheel) How did you come to be passionate about what you do?

How does one become what one is? A mixture of luck with what nature, parents and our early social environment has endowed us with and what we were able to make of it. I feel very humble about what I have been able to achieve and privileged in being able to do what I strongly care about.

Kausar Raheel) What do you wish to see more from female scientists?

More self-confidence and persistence. Don’t let anyone discourage you – women can make it!

Kausar Raheel and Esther Awodipe) What are your aspirations and advices for young female scientists?

My answer is very simple and always the same: chose your partner well! Why? To embark on a scientific career and, even more important, to sustain it, you will need the full support of your partner. As probably neither you nor your partner has already experience in juggling the precarious life-work (im)balance that awaits you in science, you might want to involve a mentor to discuss with both of you what this entails for you. Don’t fall into illusions – life is sufficiently hard, but life in science is also immensely rewarding.

Esther Awodipe) Have you experienced any challenges working in STEM as a woman? If so, how did you overcome these challenges?

My first challenge came when I applied for my first job with a professor who knew my work well. He frankly declared that he prefers a man for the position – in those days this could still be stated openly! I asked him why and he had rational arguments: sooner or later I would get married, have kids and his investment into my training would be lost as I might leave the job or be less committed. In the end, we agreed: if he finds a man whose overall qualifications are better than mine, the job should go to him. Well, I got the job! But this is not the end of the story. After two years I got married and left with my husband to New York where I started a new career. The cunning of reason was on my side after all.

Esther Awodipe) Who is your biggest inspiration and why?

Although there are many people who do great things, I had to find my own way.

Esther Awodipe) How do you motivate yourself and stay motivated?

Motivation was never a problem for me. As I said before, I feel privileged that I can do what I like to do. But I had also had to work hard to get there.

Esther Awodipe) How do you manage your work-life balance?

Taking a break when it feels necessary, getting enough sleep, keeping fit, laughing…

Ines Das Neves) Based on your experience in several areas, but particularly through your work in the European Research Council, what, to you, are the major problems with the way peer review processes are currently conducted or set up to work? Do you think there is room for much change within the frameworks for research funding and policy that are presently in place?

We worked hard at the European Research Council to set up a peer review culture unlike any other. Not that we changed the procedure, but we made huge efforts to find the best scientific minds to serve in our evaluation panels, people who were broad in their scientific knowledge and open-minded, having good judgement and looking for scientific excellence only. But nobody is exempt from unconscious bias. We carefully monitored what we observed, giving feed-back to panel members and showing them examples of where unconscious bias might have occurred.

The general problem is that the peer-review system is under immense pressure. It is bursting at the seams. Funding agencies then resort to formal mechanisms, i.e. indicators of various kinds and quantitative measures. While this alleviates stress to the system, it that can never fully replace a carefully calibrated peer-review system with good human judgment.

The solution is to differentiate much better: which funding streams can rely on light reviewing, perhaps with very simple indicators? Which funding streams need a (perhaps quantitative) preselection, followed by careful interviews with the pre-selected candidates? When should reviewers read the publications of the candidates and when is it sufficient to look only at the publication list? Various other solutions are being discussed right now, but the most important is not to rely on ‚One size fits all’.

Ines Das Neves) Why do you believe that embracing uncertainty is important to scientific research and the way its findings are presented to the general public?

As I wrote in „The Cunning of Uncertainty“ science and scientists thrive on the cusp of uncertainty. In basic or fundamental research one does not know what one will find, yet it is precisely this uncertainty that is attractive, pushing scientists into the yet unknown. Speaking to the public, one has to have the courage to admit that absolute certainty does not exist and that we all have to learn to live with probabilities. We have to communicate better that scientific knowledge is always preliminary in the sense that it will be replaced by more and better knowledge. We also have to say loud and clearly that scientific findings hold under certain conditions that can be spelled out. There is no simple and unconditional ‚yes’ or ‚no’ to many of the questions that preoccupy the public. But we can and should explain better how science works and how scientific findings are arrived at. It can be done!

Ines Das Neves) You have recently written the book, An Orderly Mess. What drove you to write about this particular subject?

This little book consists of two essays. ‚Revisisting Eigenzeit’ is based on an Inaugural lecture I was invited to give for a big research project at the Haus der Kulturen in Berlin. It is an analysis of what has changed in our experience of time since I first published my book on Time (the German title was ‚Eigenzeit’) some thirty years ago. The Central European University Press (yes, from the embattled Central European University in Budapest that is under threat of being closed) wanted to translate and publish it. They asked me to write a second essay and I thought that the topic of ‚messiness’ cuts across societal concerns and can be found in science as well. In a sense, it follows the cross-cutting  theme of uncertainty. Messiness alerts us to the dynamics of order and disorder and our involvement in generating both, but also how to deal with it.

Carolina Beppi) The educational system can be considered a ‘positive constraint’ to our creativity, providing us with the scientific knowledge and tools that spur our creative ideas. One the other hand, the educational system represents a ‘negative constraint’, limiting our research to a corrupted ‘school of thinking’, where the scientific discovery and advancement is limited by the demand and interests of the capitalist economy and market. What ‘revolutionary action’ should we enact, in your opinion, as socially aware scientists?

I don’t think that ‚revolutionary action’ is anywhere on the horizon these days. We speak about ‚responsible research and innovation’, of more sharing, better cooperation and open science. The point is that greater awareness is needed about the many complex interrelationships between science and society in a global and globalising world. To become more aware of our interdependencies, but also of our ability to act. We are neither the pawns of history, nor its masters. But we often do have greater freedom to act than we may think. I would like to see more young scientists to become what I call ‚competent rebels’.

Carolina Beppi) Currently successful industries are now applying machine learning classification and prediction techniques on consumer data to guide their market strategies and maximise their outcomes. Only those industries that are successfully integrating these softwares will survive in the economy. At that point, economical power will only become a matter of ‘who owns the biggest data’. To what extent do you agree with this statement?

This is too deterministic for me. All big technological paradigm changes have produced monopolies. They have to be broken up and regulated by the state. This is the point where we are now with Google, Amazon, Facebook and the like. I admit that it is more complicated now as the state has partly been overtaken by markets and we have to factor in the global world. But I am convinced that regulation of the ‚big data’ world will happen.

Carolina Beppi) Algorithms that extent predictions at aggregate level, the increasing accumulation of big data, but also developments in risk management, cannot protect against ‘the unpredictable’ – and the 2008 financial crisis is an exemplification. Do you believe the development and integration of AI intelligence will soon lead to another worldwide economical and social risks in the context of both employment and security?

The risks are there, undoubtedly.

Carolina Beppi) Rita Levi-Montalcini was one of the greatest scientific minds of the 20th century. She believed ‘Women have always had to fight doubly. They always had to carry two weights, the private and the social. Women are the vertebral column of society’. What is your idea in this regards?

Rita Levi-Montalcini was right, but we have to challenge men more and better to share the burden. With humanity stumbling into an uncertain and artificial future in which humans and non-human artefacts will mix and mingle in unforeseen ways, new forms of living together will evolve. Perhaps much of the aggressive misogynic behaviour that we see today is the last rear-guard fight of a patriarchy that will no longer have a place in the future. Let us remember: whatever life forms will evolve depends also on us. My hope is that they will be more inclusive and based on mutual respect.

Interview with Professor Jackie de Belleroche: ‘Just be yourself, follow your dream’

Professor Jackie de Belleroche leads the Imperial College London research group that has a strong commitment to investigate on Amyotrophic Lateral sclerosis (ALS) through molecular genetics, expression profiling in spinal cord and through the use of experimental models to develop new therapeutic approaches.

The key aims of this new blog are to enhance the curriculum and innovate pedagogy, highlight the contribution of women in academia within and outside the College, and engage and inspire the society. The founder and editor of the blog is Dr Stefano Sandrone, Teaching Fellow within the Faculty of Medicine, and the contributors are Imperial’s MSc Translational Neuroscience students.

Leire Melgosa) What made you choose science and the area of research you work in?

I was always deeply fascinated by Molecular Biology from DNA to medical research.

Caroline Schaufelberger) What were the main considerations you made when taking your career forward in research rather than in a clinical environment?

I was lucky that my early research was always relevant to neurological disorders such as epilepsy and stroke. This background helped me to gain a lectureship, a joint appointment in Biochemistry and Neurology, which provided the perfect environment to pursue research in clinical Neuroscience.

Leire Melgosa) What have been the most challenging part of your career and the most satisfying one so far?

In common with many others, the most challenging stage was finding an established position that would enable me to develop as an independent researcher. For me, this came with the award of a Mental Health Foundation Fellowship. Research is full of surprises, but each new discovery, however small, is very satisfying. However, even more than this, is to see the success of members of my research group in setting up their own research teams and establishing themselves in their various chosen careers.

Ryan Dowsell) How realistic is it to think that gene mutations play a much more significant role in motor neurone disease (ALS) than we currently believe?

Understanding how gene mutations cause disease in families has had a phenomenal effect on our ability to define the processes that underpin disease processes and also occur in sporadic cases, and are therefore targets for therapeutic intervention. This is, of course, only part of the story, as ALS is an adult-onset disorder and effects of ageing play an important role and an increasing number of DNA variants are being discovered that modify gene function and act as risk factors. Overall, multiple factors will undoubtedly contribute to the final evolution of disease, e.g. age at onset and duration of disease.

Claudia Ghezzou) Throughout you career, what have been the motivations and incentives that have kept you focused in your impact as a researcher regardless of the possible difficulty of the processes or discouraging results from the research carried out? 

I have always been committed to finding out the basis of disease both in neurodegenerative and psychiatric disorders. This is never ending, whatever the setbacks, the challenge is always there to find a way forward. Discouraging results may even provide a greater depth of understanding and lead to a more fruitful approach.

Shinil Raina) How has your experience as a woman in science changed since when you started as an undergrad?

Jessica Hain) Did you encounter any difficulties in your pursuit to be a female scientist, and do you think attitudes have changed over the years? If so, to what extent?

Of course attitudes have changed monumentally which is a major achievement, but there is still room for improvement. As a scientist, I did not think of myself as being different, being female. Travelling to international conferences, where female representation amongst the speakers is low, just makes you realise how much has been achieved.

Caroline Schaufelberger) What do you think are the main challenges for women in science and what has your experience taught you that would aid the next generation tackle these challenges?

Danielle Kurtin) How do you balance work as well as motherhood?

These are of course relevant to all walks of life. The framing of your question is absolutely correct to address the issue of balancing work and motherhood. Once you return from maternity leave you need to find a balance, allocate your time as much as possible equally to your work and your family. There are many options available for childcare and universities like Imperial have many facilities available and provide other types of support, which all help to make life easier at what would otherwise be a challenging time. My daughters have greatly benefitted from attending the crèche and nursery which are highly recommended but many other options are available.

Ryan Dowsell) How has working at Imperial College London helped to shape your career as a woman in science?

Imperial is a very dynamic and supportive place to work, whether male or female.

Caroline Schaufelberger) Especially in our MSc cohort there is a higher percentage of women compared to men, what do you see is the importance of more women entering a career in science?

Ryan Dowsell) Throughout my undergraduate and postgraduate studies, I’ve noticed how the classes have always included more female than male students. So from your experience, what do you think is causing a gender disparity between the roots of STEM and the managerial positions?

Across UK Universities as a whole, there are similar gender differences in particular subjects, more females in biological subjects, more males in engineering. Medicine and chemistry are more evenly balanced. The disparity may be based historically on traditional attitudes, but there have been some marked changes in some subjects, such as Medicine, to reach an equality between males and females compared to a few decades ago. I am encouraged to see more women embarking on careers in sciences, where there will be increasing opportunities available.

Jessica Hain) Do you have any advice for neuroscience students?

If you have a passion for a subject, you should pursue it.

Leire Melgosa) Do you have specific advices for young female scientists (i.e. a hard truth or something we tend to worry about but we should not)?

Just be yourself, follow your dream. There are always difficult times, whether male or female, but there is always a way through.

 

Photography credit: Jackie King

Cognition, depression and cognitive changes in Major Depressive Disorder: a brief consideration

Carolina received her Psychology, Clinical and Cognitive Neuroscience bachelors degree from Royal Holloway University of London and she has recently obtained a MSc degree in Translational Neuroscience from Imperial College London: Cognition is extremely fascinating. It is my belief that understanding how we learn is the key to self-actualisation.

 

Cognition is a term that refers to all the mental processes involved in the interpretation of the environment, including overt behaviours and emotional states, by mean of sensory experience (Neisser, 2014). For example, while watching a rugby match, we may interpret a physical contact between two players as being painful based on the visual information of a bleed and on the emotional reaction of a cry. The mental processes supporting the production of deliberate actions are also components of cognition (Neisser, 2014). Reaching for an object, for instance, would require focused attention to the target and online adjustments of the body position in the space relatively to the object.

Cognitive abilities are a determinant aspect of quality of human life. Reports suggest that cognitively skilled children obtain more prestigious occupations later in life (Cheng & Furnham, 2012) and a significant portion of variability in academic achievement in adulthood is explained by general cognitive ability (Rohde & Thomposon, 2007). In the elderly population, good cognitive functioning is associated with more satisfactory interpersonal relationships (Watanabe et al., 2016), engagement in social activities, hobbies, sports, volunteering, and generally more diversified daily activities (Fu et al., 2018).

Aging is accompanied by a cognitive deterioration that differently affects fluid and crystallised abilities (Cattell, 1943). The former comprise reasoning skills employed to solve mental operations and tasks (Murman, 2015), such as inferring the fastest bus route to approach a specific city district. Crystallised abilities constitute instead cumulative knowledge (i.e. facts) and experience acquired in the course of time (Murman, 2015). In 2009, a large cross-sectional study revealed that while fluid skills constantly deteriorate from late adolescence, crystallised abilities increment along with age, reaching a plateau in the 60s (Salthouse, 2009).

Cognition is, in part, genetically determined (Hill et al., 2014). However, a wide range of modifiable environmental factors can ‘accelerate’ or ‘attenuate’ cognitive decline. Interpersonal relationships contribute to maintain cognitive health by promoting social identification and support (Haslam et al., 2016). Furthermore, cognitive functioning is supported by higher levels of education, socioeconomic status and intellectual activity (Parisi et al., 2012). Nonetheless, various environmental risk factors can negatively affect cognition, such as smoking (Waisman Campos et al., 2016), a poor diet (Shatenstein et al., 2012) and low levels of physical activity (Kelly et al., 2014).

Cognitive functions can also be affected by depression. Major depressive disorder (MDD) is a common psychiatric disorder that negatively affects mood, thoughts and behaviours, compromising the ability to function both at work and at home. It is characterised by symptoms including low mood, loss of interest, fatigue, appetite changes, suicidal thoughts, difficulty thinking and irritability, for a period of time of at least 2 weeks (American Psychiatric Association, 2013). Major depression is one of the most disabling illnesses: it contributes to early mortality causing 60% of worldwide suicides (World Health Organization, 2009) and it has elevated annual pharmaceutical costs (Kessler, 2012), thus constituting a major global social and economic concern.

The onset of MDD typically occurs in late adolescence, and it is more prevalent among women than men (Hasin et al., 2018). It annually affects ~6.7% individuals, and ~16.6% of the population experience it at least once it in their life (Kessler et al., 2005). Importantly, depression not only represents a risk factor of accelerated cognitive decline, but it affects cognitive functioning in the everyday-life experience. Depressed individuals are more likely to ‘misinterpret’ neutral faces as expressing anger (Watters & Williams, 2011) compared to healthy controls. The ‘tendency’ towards negative emotions in depression is moreover accompanied by a lower ‘reactivity’ to positive stimuli, whereby hedonic pictures are considered to be less pleasant and less arousing compared to healthy subjects (Sloanab et al., 1997).

Furthermore, depression is generally linked to deficits of memory (Burt et al., 1995) including a decreased recognition and retrieval of previously learned words (Brand et al., 1992), visuomotor ability, such as a reduced horizontal eye-movements span (Deijen et al., 1993), but also mental flexibility (Airaksinen et al., 2004), language fluency (Reischies & Neu, 2000), abstract reasoning (Naismith et al., 2003) and decision-making, with an increased risk of impulsively engaging in pleasurable activities with harmful consequences (Chamberlain & Sahakian, 2006).

What is the impact of existent therapies on depression and cognition?

Recently, the effect of three different antidepressant drugs has been tested on patients with MDD and diminished functioning in seven cognitive domains including attention, verbal memory, mental flexibility, decision-making and information-processing (Shilyansky et al., 2016). The results showed that while all the antidepressants succeeded in improving mood-related symptoms, their effectiveness on cognition was limited to only two domains: mental flexibility and executive functions, namely organizing and planning skills. Talking treatments, such as the cognitive behavioural therapy, have been shown to improve the clinical symptoms of depression (Twomey et al., 2014), although their impact on cognitive dysfunctions are yet to be explored.

This is an exciting research avenue for the future: further investigations are required to delineate the distinct components of cognition, to elucidate the nature and extent of the cognitive changes in depression, as well as, to develop novel approaches to address specific deficits.

References

Airaksinen, E, Larsson, M, Lundberg, I and Forsell, Y (2004) Cognitive functions in depressive disorders: evidence from a population-based study. Psychological medicine34(1):83-91.

American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5). American Psychiatric Pub.

Brand, AN, Jolles, J and Gispen-de Wied, C (1992) Recall and recognition memory deficits in depression. Journal of affective disorders25(1):77-86.

Burt, DB, Zembar, MJ and Niederehe, G (1995) Depression and memory impairment: a meta-analysis of the association, its pattern, and specificity. Psychological bulletin117(2): 285.

Cattell, RB (1943) The measurement of adult intelligence. Psychological Bulletin40(3):153.

Chamberlain, SR and Sahakian, BJ (2006) The neuropsychology of mood disorders. Current psychiatry reports8(6):458-463.

Cheng, H and Furnham, A (2012) Childhood cognitive ability, education, and personality traits predict attainment in adult occupational prestige over 17 years. Journal of Vocational Behavior81(2):218-226.

Deijen, JB, Orlebeke, JF and Rijsdijk, FV (1993) Effect of depression on psychomotor skills, eye movements and recognition-memory. Journal of affective disorders29(1): 33-40.

Fu, C, Li, Z and Mao, Z (2018) Association between social activities and cognitive function among the elderly in China: a cross-sectional study. International journal of environmental research and public health15(2): 231.

Kelly, ME, Loughrey, D, Lawlor, B.A., Robertson, I.H., Walsh, C. and Brennan, S. (2014) The impact of cognitive training and mental stimulation on cognitive and everyday functioning of healthy older adults: a systematic review and meta-analysis. Ageing research reviews15:28-43.

Hasin, DS, Sarvet, A.L., Meyers, JL, Saha, TD, Ruan, WJ, Stohl, M and Grant, BF (2018) Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA psychiatry75(4): 336-346.

Haslam, C, Cruwys, T, Milne, M, Kan, CH and Haslam, SA (2016) Group ties protect cognitive health by promoting social identification and social support. Journal of aging and health28(2):244-266.

Hill, WD, Davies, G, Van De Lagemaat, LN, Christoforou, A., Marioni, RE, Fernandes, CPD, Liewald, DC, Croning, MD, Payton, A, Craig, LC and Whalley, LJ (2014) Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins. Translational psychiatry4(1):e341.

Kessler, RC (2012) The costs of depression. Psychiatric Clinics35(1):1-14.

Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR and Walters, EE (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry62(6):593-602.

Leykin, Y, Roberts, CS and DeRubeis, RJ (2011) Decision-making and depressive symptomatology. Cognitive therapy and research35(4):333-341.

Murman, DL (2015) The impact of age on cognition. Seminars in hearing 36(3): 111. Thieme Medical Publishers.

Naismith, SL., Hickie, IB., Turner, K, Little, CL, Winter, V, Ward, PB, Wilhelm, K, Mitchell, P and Parker, G (2003) Neuropsychological performance in patients with depression is associated with clinical, etiological and genetic risk factors. Journal of clinical and experimental neuropsychology25(6): 866-877.

Neisser, U (2014) Cognitive psychology: Classic edition. Psychology Press.

Parisi, JM, Rebok, GW, Xue, QL, Fried, LP, Seeman, TE, Tanner, EK, Gruenewald, TL, Frick, KD and Carlson, MC (2012) The role of education and intellectual activity on cognition. Education, 15:19

Reischies, FM and Neu, P (2000) Comorbidity of mild cognitive disorder and depression–a neuropsychological analysis. European archives of psychiatry and clinical neuroscience250(4):186-19

Rohde, TE and Thompson, LA (2007) Predicting academic achievement with cognitive ability. Intelligence35(1):83-92.

Salthouse, TA (2009) Decomposing age correlations on neuropsychological and cognitive variables. Journal of the International Neuropsychological Society15(5):650-661.

Shatenstein, B, Ferland, G, Belleville, S, Gray-Donald, K, Kergoat, MJ, Morais, J, Gaudreau, P, Payette, H and Greenwood, C (2012) Diet quality and cognition among older adults from the NuAge study. Experimental gerontology47(5):353-360.

Shilyansky, C, Williams, LM, Gyurak, A, Harris, A, Usherwood, T and Etkin, A (2016) Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study. The Lancet Psychiatry3(5):425-435.

Twomey, C, O’Reilly, G and Byrne, M (2014) Effectiveness of cognitive behavioural therapy for anxiety and depression in primary care: a meta-analysis. Family practice32(1): 3-15.

Waisman Campos, M, Serebrisky, D and Mauricio Castaldelli-Maia, J (2016) Smoking and cognition. Current drug abuse reviews9(2):76-79.

Watanabe, K, Tanaka, E, Watanabe, T, Chen, W, Wu, B, Ito, S, Okumura, R and Anme, T (2016) Association between Social Relationships and Cognitive Function among the Elderly. Public Health Research6(2):59-63.

Watters, AJ and Williams, LM (2011) Negative biases and risk for depression; integrating self‐report and emotion task markers. Depression and anxiety28(8):703-718.

World Health Organization (2009) Depression: A global public health concern, Accessed 28 May 2018, <http://www.who.int/mental_health/management/depression/who_paper_depression_wfmh_2012.pdf>

 

Picture credits: Wellcome Collection

Neuroscience behind that perfect cup of morning coffee

Yi-Ting Wang (Tina) is a prospective neuroscientist at the starting point of her scientific career. She uses her little grey cellstrying to solve some of the 21st centurys most fascinating problems in Imperial College London. Like the entomologist in search of colourful butterflies, my attention has chased in the gardens of the grey matter cells with delicate and elegant shapes, the mysterious butterflies of the soul, whose beating of wings may one day reveal to us the secrets of the mind.’  -Santiago Ramon y Cajal

If you are an avid coffee drinker like me, the best way to kick a day off is brewing that one tasty cup of sweet-smelling morning coffee, or grab one at your favourite coffee shop on the way to the workplace. During the day, you probably need some more cups of coffee to keep you going. The active ingredient in coffee is caffeine, the most widely used psychoactive drug in the world. How does the whole process actually work, and how does caffeine affect our brain? Lets reveal the secret of this magical brain fuel from a neuroscientific perspective.

How does caffeine act on our brain?

It’s normal to grow tired as the day progresses because our brains naturally secrete a molecule called adenosine. Briefly, adenosine influences attention, alertness, and sleep. Adenosine builds up in our brain and when it reaches a certain level, our body knows its bedtime. In simple words, caffeine hijacks this system by competing with adenosine for the receptors. By blocking the action of adenosine, we end up feeling more alert and awake (Ribeiro and Sebastião, 2010). It is worth noticing that considerable amount of research reported that coffee can improve cognitive performance and decrease the risk for neurodegenerative disease such as Parkinsons disease (PD) and Alzheimers disease (AD).

Coffee every day, keep doctors away?

Three different epidemiological studies performed in Spain (Jimenez-Jimenez et al., 1992), Germany (Hellenbrand et al., 1996) and Sweden (Fall et al., 1999) reported an inverse, dose-responsive relationship between coffee consumption and the risk of developing PD. Two meta-analyses also showed that the risk of developing PD decreased by 31% (Hernan et al., 2002) and 25% (Costa et al., 2010) respectively in coffee drinkers compared to non-coffee drinkers. However, a more recent case control study suggested only a weak inverse association between coffee intake and the risk of PD (van der Mark et al., 2014). Though the debate is still going on, experimental studies have identified a possible mechanism behind caffeines potential preventative role in the development of PD.

Classically the primary pathology of PD involves the degeneration of dopaminergic neurons that originate in the substantia nigra and project to the striatum. Striatum is a principal component of the basal ganglia. Common PD symptoms such as slow movement, tremors, and rigidity are resulted from the cell death in basal ganglia and their connecting pathways. Low dose of caffeine was shown to mainly antagonise adenosine A2A receptors. The blockade of A2A receptors stimulates dopaminergic D2 receptors and as a result increases motor activity and improves motor deficits in PD models (Fenu and Morelli, 1998), (Kuwana et al., 1999).

A wealth of studies suggested that regular and moderate coffee intake over a lifetime reduces the risk of developing AD. A study published in 2012 gathered preclinical and clinical evidence and found a protective role of caffeine against AD. Results showed that caffeine can reduce risk, or delay onset of dementia. The effect was particularly evident in mild cognitive impairment patients (Cao et al., 2012). Among the most prominent studies, a case-control study showed that caffeine consumption was inversely associated with AD development (Maia and de Mendonça, 2002). In CAIDE study, 1409 elderly were analysed after a 21 yearsfollow-up. Coffee consumption in midlife was shown to decrease the risk of AD and dementia, with the lowest risk (65% decrease) found in people who drank 35 cups/day (Eskelinen et al., 2009). Animal studies helped us identify the possible mechanisms behind coffees effects on AD risk. Dr. Gary Arendash and colleagues found that caffeine improved learning and memory ability of transgenic mice and reduced the concentration of β-amyloid and presenilin in the hippocampus, the main brain structure involved in memory (Arendash et al., 2006). Caffeine also showed to reduce inflammatory mediators, which is another possible explanation of why it could ameliorate AD progression (Arendash et al., 2009; Cao et al., 2009).

How much coffee can we drink?

We have discussed some effects of caffeine on the brain based on different research findings. However, so far most of the evidence for both benefits and adverse effects of caffeine were derived mainly from observational studies, which means we couldnt draw any conclusion of caffeines causal effect on brain function. This awaits further randomised-controlled studies to confirm. Over the last decade, health authorities around the world have concluded that coffee/caffeine consumption is not harmful at levels of 300-500 mg daily (around 3-5 cups of coffee) (Nehlig, 2016). Back to the question, how much can we drink? Just remember moderation is the key, and be a happy coffee drinker!

 

References

Arendash GW, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H (2009) Caffeine reverses cognitive impairment and decreases brain amyloid-β levels in aged Alzheimers disease mice. Journal of Alzheimers Disease 17(3):661-80.

Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J (2006) Caffeine protects Alzheimers mice against cognitive impairment and reduces brain β-amyloid production. Neuroscience 142(4):941-52.

Cao C, Cirrito JR, Lin X, Wang L, Verges DK, Dickson A, Mamcarz M, Zhang C, Mori T, Arendash GW, Holtzman DM, Potter H (2009) Caffeine suppresses amyloid-β levels in plasma and brain of Alzheimers disease transgenic mice. Journal of Alzheimers Disease 17(3):681-97.

Cao C, Loewenstein DA, Lin X, Zhang C, Wang L, Duara R, Wu Y, Giannini A, Bai G, Cai J, Greig M, Schofield E, Ashok R, Small B, Potter H, Arendash GW (2012) High blood caffeine levels in MCI linked to lack of progression to dementia. Journal of Alzheimers Disease 30(3):559-72.

Costa J, Lunet N, Santos C, Santos J, Vaz-Carneiro A (2010) Caffeine exposure and the risk of Parkinsons disease: a systematic review and meta-analysis of observational studies. Journal of Alzheimers Disease 20 Suppl 1:S221-38.

Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M (2009) Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. Journal of Alzheimers Disease 16(1):85-91.

Fall PA, Fredrikson M, Axelson O, Granérus AK (1999) Nutritional and occupational factors influencing the risk of Parkinsons disease: a case-control study in southeastern Sweden. Movement Disorders 14(1):28-37.

Fenu S. and Morelli M (1998) Motor stimulant effects of caffeine in 6-hydroxydopamine-lesioned rats are dependent on previous stimulation of dopamine receptors: a different role of D1 and D2 receptors. The European Journal of Neuroscience 10(5):1878-84.

Hellenbrand W, Seidler A, Boeing H, Robra BP, Vieregge P, Nischan P, Joerg J, Oertel WH, Schneider E, Ulm G (1996) Diet and Parkinsons disease. I: A possible role for the past intake of specific foods. Results from a self-administered food-frequency questionnaire in a case-control study. Neurology 47(3):636-43.

Hernán MA, Takkouche B, Caamaño-Isorna F, Gestal-Otero JJ (2002) A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinsons disease. Annals of Neurology 52(3):276-84.

Jimenez-Jimenez FJ, Mateo D, Giménez-Roldan S (1992) Premorbid smoking, alcohol consumption, and coffee drinking habits in Parkinsons disease: a case-control study. Movement Disorders 7(4):339-44.

Kuwana Y, Shiozaki S, Kanda T, Kurokawa M, Koga K, Ochi M, Ikeda K, Kase H, Jackson MJ, Smith LA, Pearce RK, Jenner PG (1999) Antiparkinsonian activity of adenosine A2A antagonists in experimental models. Advances in Neurology, 80:121-3.

Maia L and de Mendonça A (2002) Does caffeine intake protect from Alzheimers disease? European Journal of Neurology 9(4):377-82.

Nehlig A (2016) Effects of coffee/caffeine on brain health and disease: What should I tell my patients? Practical Neurology 16(2):89-95.

Ribeiro JA and Sebastião AM (2010) Caffeine and adenosine. Journal of Alzheimers Disease 20 Suppl 1:S3-15.

van der Mark M, Nijssen PC, Vlaanderen J, Huss A, Mulleners WM, Sas AM, van Laar T, Kromhout H, Vermeulen R (2014) A Case-Control Study of the Protective Effect of Alcohol, Coffee, and Cigarette Consumption on Parkinson Disease Risk: Time-Since-Cessation Modifies the Effect of Tobacco Smoking. PLoS One 9(4):e95297.

Advanced reading

Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacological Reviews 51(1):83-133.