Science Week 2018: The Rosalind Franklin Lecture at the ISMB Symposium

Dr Clare Sansom reports on Birkbeck’s annual Rosalind Franklin Lecture, delivered this year as part of the biennial Institute of Structural and Molecular Biology (ISMB) Symposium. The lecture was delivered by Berkeley’s Professor Eva Nogales, a distinguished scholar in electron microscopy research.

Professor Eva Nogales (right) with Birkbeck’s Professor Nick Keep

Since 2016, Birkbeck has held an annual lecture named in honour of perhaps the most famous woman scientist ever to work there: Rosalind Franklin, whose extraordinary, meticulous experimental work was a necessary part of solving the structure of DNA. This lecture is part of Birkbeck’s commitment to the Athena SWAN equality initiative, and is it given by a woman scientist distinguished in one of the disciplines represented there.

The 2018 lecture differed from its predecessors in forming part of both Birkbeck’s annual Science Week and the eighth ISMB Symposium. The Institute of Structural Molecular Biology (ISMB) is a centre of excellence, founded in 2003 to promote and integrate multi-disciplinary research in molecular, cell and structural biology in Birkbeck and its much larger neighbour, UCL. It holds a varied programme of events for faculty members, research staff and students; symposia, held in ‘even years’, are intensive conferences, generally held over two days and featuring talks from international research leaders.

This symposium was held over two afternoons on Monday 18 and Tuesday 19 June, with the Rosalind Franklin lecture as the last one on the first day. In planning the symposium, its organisers chose to highlight one technique among all those available for researchers at the ISMB: electron microscopy, as used to study the atomic structures of large protein complexes and ‘molecular machines’. The Institute’s director, Gabriel Waksman, highlighted Birkbeck’s acquisition of a new and very powerful electron microscope – a Titan Krios – in his introduction as ‘something to celebrate’. According to the School of Science Facebook page, Birkbeck’s Department of Biological Sciences is the smallest UK university department to house such a powerful microscope, and it is only through the ISMB that it is able to punch so far above its weight. And the Rosalind Franklin lecturer, Eva Nogales from the University of California in Berkeley, was only one of several distinguished proponents of this technique to present their research during the symposium.

Few women have achieved as much in electron microscopy research as Nogales. Following a short introduction by Professor Nicholas Keep, Dean of the Faculty of Science at Birkbeck, she began her Rosalind Franklin lecture with thanks. She paid tribute to two of the distinguished researchers present, Helen Saibil and Ken Holmes, describing Saibil, the Bernal Professor of Structural Biology at Birkbeck, as an ‘inspirational’ pioneering woman in electron microscopy. Holmes, who had given one of the previous talks at the symposium, worked with Rosalind Franklin as a PhD student at Birkbeck in the 1950s and went on to make ground-breaking discoveries about the structure of the muscle protein, actin.

Nogales’ main theme during her lecture was her lab’s efforts to decipher the structures of several large, multi-protein complexes that are involved in the process of gene expression. The different types of cells in our bodies – with a few odd exceptions, such as cancer cells – all contain exactly the same DNA in the chromosomes in the cell nucleus. What makes a brain cell differ from a bone cell or a heart call is how the information carried by the genes on those chromosomes is expressed in the functional molecules, mainly proteins.  Only a fraction of the genes in a genome are expressed in a given cell at any particular time. Gene expression is the term given to this incredibly complex and exquisitely sensitive process, which can be divided into two stages expressed simplistically as ‘DNA to RNA’ and ‘RNA to protein’. Work in the Nogales lab focuses on two protein complexes that are involved in the first sub-process, the transcription of the DNA sequences of genes into RNA. These bear the rather cumbersome names of polycomb repressive complex 2 (PRC2) and transcription factor II D (TFIID).

If the DNA in each human chromosome could be stretched out it would measure tens of centimetres in length. It is packed and compressed to fit into the microscopic cell nucleus by winding around histone proteins to form circular units of structure called nucleosomes. Proteins in the ‘transcription machinery’ can only access the DNA to start gene expression if these are loosely packed. PRC2, as its full name implies, represses this process: it does so by adding methyl groups to the alkaline lysine residues of the histones, making the nucleosomes pack more tightly together. The protein complex therefore forms an ‘on-off switch’ for gene expression. Disrupting its function can lead to the uncontrolled cell growth and multiplication that is characteristic of cancer cells and it is therefore a useful target for the design of anti-cancer drugs.

Nogales explained that PRC2 is a very large protein complex and that determining its structure using electron microscopy presented a considerable challenge. The first structures, obtained before the ‘resolution revolution’ in this technique, could only show separate protein molecules as ‘blobs’: later, better structures that revealed the positions of individual atoms proved that these were ‘accurate but not very precise’. The complex is now known to exist in several distinct structural states and to be able to add methyl groups (‘active’) in two of them. The main difference between these is in the position of one helix, which is bent against the rest of the molecule in the ‘compact active’ conformation but straightens away from it in the ‘extended active’ one.  PRC2 binds to two protein co-factors in ways that mimic the binding of the flexible ‘tails’ of the histone proteins in methylated and unmethylated forms respectively.

She then showed some even more impressive structures to explain how the complex interacts with nucleosomes. One complex binds between a pair of nucleosomes, and as long as the DNA that links the two is the right length, binding the first nucleosome positions the second so that the right amino acids are brought into the right position in the PCR2 active site for methylation to occur efficiently.

The second complex discussed, TFIID, is active exactly when PRC2 is not, as its presence is necessary to begin the process through which DNA is transcribed into RNA. This begins with the step-by-step assembly of proteins close to the position on the DNA where transcription is due to start, forming a ‘preinitiation complex’. TFIID is the first component of this complex to assemble, and this ‘nucleates’ the complex by recruiting other transcription factors so RNA synthesis can begin. Nogales described distinctive structures of parts of the preinitiation complex obtained by members of her group, finishing by showing some unpublished work on its structure and dynamics that included this vital component. If this fascinating lecture has inspired the many young electron microscopists in the audience as much as Helen Saibil’s work inspired Nogales, then the future of the discipline will be in good – and often female – hands.

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Self-representation: do you really know yourself?

Satwat Bashir, MSc Cognition and Computation student, reports on Dr Lara Maister’s Science Week talk.

Dr Lara Maister

In our daily life, we spend a great deal of time focusing on ourselves; whether we are buying shoes, preparing for a job interview, posting on social media or impressing a date. But how exactly are we aware of ourselves? Do we ever think about it? Ehh… no.  When Donald Trump described himself as a ‘not smart, but a genius and a very stable genius’, he was accused of being mentally unhealthy and lacking self-awareness. But scientific research is beginning to reveal that people’s self-awareness is not as accurate as we think, despite the fact that we are the only ones in the universe with direct access to every thought and feeling we come across. Lara Maister’s talk took a very thought-provoking, curious and engaging way to share the science behind our ‘selfhood’. What could be more interesting than to know about your own body and mind?

At the start, Lara gave a general introduction on how we perceive the ‘self’. She made a distinction between two often-related forms of ‘self’, namely; bodily-self and conceptual-self. She explained the conceptual-self as concerning our beliefs, feelings, preferences and attitudes, and that its formation and development is strongly related to social interactions and comparisons. In contrast to this, bodily-self is understood through our subjective experiences of bodily ownership and physical appearance. For example; I experience my body moving when I tell it to move, and I always have a mental image of how I am appearing in the world. Interesting!

Lara went on explaining the cognitive neuroscience story behind these selfhoods and how these two forms are malleable and can influence each other, eventually changing the whole ‘self’. First focusing on the ‘bodily self’, she discussed a rare neurological condition that leads to the loss of the sense of bodily ownership which has motivated the investigation into the nature and processing behind our ‘self-hood’.

The rubber hand illusion is one of the methods used to probe the ‘bodily self’. Researchers were able to induce a feeling of ownership over a prosthetic hand, using synchronous visual-tactile stimulation. She explains that it is basically the result of the brain’s ability to synchronize the touch felt on real hand with the touch seen on the prosthetic hand. This discovery extended the scope of bodily illusions investigations and researchers are now able to produce and observe the similar effects with other senses that result in illusory body ownership, like voice illusions and face illusions.

Lara kept the curiosity high and went on unfolding the mysteries and shared the studies in which she and her team tested how accurate people are when they picture their appearance in their mind, compared to what they actually look like. She uses a task, which allows participants to develop a ‘self-portrait’ via the computer, which represents how they think they look in their mind’s eye. The results showed people are generally good at predicting their facial characteristics; for example, if someone has a bold nose or striking eyes, their self-portrait will have these features, so in general, people are well aware of how they look like in the real world.

The most attention-grabbing result from her investigation demonstrated that participants’ beliefs about their personality traits influenced what their self-portraits looked like. For example, if they think they are considered neurotic in their social circles, then their self-portrait contains such features that look ’neurotic’ – irrespective of their real facial features. A very interesting example shown by Lara was of two females which are very alike in their physical appearance, but they have exactly opposite self-conception about themselves; one thinks she is attractive and trustworthy and other thinks she is unattractive and untrustworthy. Importantly, they made very different self-portraits too; the one who believed she was unattractive and untrustworthy saw her face as being much less attractive and agreeable than the participant who was more self-confident. Why is this so? Another mystery! Lara explained that researchers believe our feelings and beliefs about ourselves affect our bodily mental representation of our own appearance.

But how is self-esteem affecting the representation of our bodies, as well as our faces? Lara shared another investigation focusing on self-esteem and our mental images of our body shape. The results are very fascinating and confirm the previous finding that self-esteem plays a significant role in a person’s beliefs about themselves and that most of the time we are inaccurate in determining how we look. Specifically, the researchers measured the hip size of people’s mental pictures of their own bodies, and what they thought a ‘normal’ body looked like. Not only were people’s mental pictures of their body shape quite inaccurate, the data pattern depicts that hip size is inversely related to self-esteem; the larger the hip size of the self-portrait, the lower the self-esteem. So, what’s going on with our self-esteem, and how can we know our true selves?

The studies explain a variety of phenomena from our daily life, ranging from our choices when buying clothes, to our social worth and comparisons. Lara excellently explained a potential method to look into the self in different personality disorders, as well as mental disorders such as dysmorphic disorders and eating disorders.

The investigations are still ongoing and we are anxiously waiting for the new findings so we can better understand and welcome our true selves!

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Volcanoes without borders

Neill Marshall, undergraduate Geology student, discusses a recent event on diplomacy in scientific research, as part of Birkbeck’s 2018 Science Week.

Studying Earth Sciences offers unique opportunities to travel to remote and exciting places around the world, and this has certainly been the case for geophysicist Dr James Hammond. As part of the #BBKScienceWeek 2018 talks, Dr Hammond presented his work on Mount Paektu, a remote volcano straddling the North Korean and Chinese border. He spoke of the unique experience of studying a poorly understood active volcano capable of catastrophic eruptions that has a significant cultural importance to all Koreans.

The cultural significance of Mount Paektu

Mount Paektu is the highest point on the Korean peninsula with importance to all Koreans as a strong-hold against the Japanese invasion. Dr Hammond described how it is the symbolic birthplace of the communist revolution and Kim Jong-il was thought to have been born there. Now many North Koreans go on a pilgrimage to Mount Paektu to rejoice in their leader’s birthplace. Dr Hammond showed videos of performances of the mass gymnastics at the Arirang Festival depicting Mount Paektu and of school children singing songs about the volcano.

Geopolitics and science diplomacy

Studying a volcano in a politically volatile region rarely visited presented Dr Hammond and his colleagues with logistical and diplomatic challenges. Following the increased activity at Mount Paektu, North Korea called out for collaboration with world scientists. It took two years of negotiation between the UK, US and North Korean governments with involvement from the Royal Society and the AAAS before a joint North Korean-UK scientific expedition could be mounted.

Dr Hammond and his colleagues became the first western scientists to visit the Mount Paektu volcano observatory. Dr Hammond described how the project ultimately enabled scientific communication with North Korean scientists allowing knowledge to be shared between this politically isolated nation and the wider scientific community outside North Korea.

Scientific interest in Mount Paektu

Dr Hammond gave a brief background on the eruptive power of Mount Paektu describing the last large eruption in 946AD as one of the biggest eruptions in human history. He described colossal eruption, bigger than Krakatoa in 1883 and on a similar scale to the Tambora eruption in 1815, with deadly lahar and pyroclastic flow deposits in the region.

Despite the scale of the 946AD eruption little is known about the volcano. It does not lie on a tectonic plate boundary unlike the vast amount of volcanoes on Earth.

Recent activity has been observed at the volcano in the form of earthquakes, increased gas emissions and deformation of the volcano. These are key indicators that the magmatic plumbing system is recharging.

The deployment of seismometers in a linear array was an attempt to use seismic waves to image the Earth’s crust near to Mt Paektu. He explained the processes involved in deployment; meeting local farmers, dignitaries and North Korean scientists; dealing with mountain weather; and travelling in this remote region.

Dr Hammond explained how seismic waves can be utilised to image the Earth in a similar way to a CT scan of a human body. From this method of imaging, a low seismic velocity zone was found 7km beneath the surface was found. Combined with other analysis of seismic velocities the results suggest the presence of fluid (likely magma) in the crust beneath the volcano.

However, more research needs to be done to fully understand the volcano with the key question of why this volcano is present in this region is still yet to be answered. Dr Hammond is planning an additional wider deployment of seismometers (potentially in 2019) to try and answer this question.

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How can cognitive neuroscience build resilience in breast cancer patients?

This post was contributed by Bethany Chapman, PhD candidate at Birkbeck. From October she will be working with the Building Resilience in Breast Cancer Centre (BRiC) to investigate ‘The efficacy of neurocognitive training on improving the processing efficiency and long-term quality of life of breast cancer survivors returning to work.’ Bethany attended Professor Derakshan’s Birkbeck Science Week talk on Thursday 21 June.

Breast cancer and its impact on emotional and cognitive health

Breast cancer is the most prevalently diagnosed form of malignancy amongst women, with recent figures revealing that a new case is diagnosed every 10 minutes in the UK. Given, its exceptionally high prevalence (75% increase since 1970s) breast cancer is currently considered across the world to be one of the most leading causes of health concern. Interestingly, evidence has denoted a significant increase in the number of younger pre-menopausal women being given a diagnosis. In particular, younger women appear to be diagnosed with more aggressive forms of breast cancer reflective of a higher grade (higher rate of cell multiplying) and stage tumour.

At present, breast cancer is targeted by a diverse range of interventions and treatments including, surgery (mastectomy), chemotherapy and/or radiotherapy as well as endocrine therapy. Whilst these interventions have greatly decreased the mortality rate most women that enter breast cancer survivorship following the completion of active treatment experience both emotional and cognitive vulnerability.

Professor Nazanin Derakshan revealed that women frequently report experiencing a range of emotional symptomologies (vulnerabilities) including:

  • Chronic anxiety and depression
  • Post-traumatic stress disorder (PTSD)
  • Intrusive thoughts regarding breast cancer recurrence
  • Poor quality of life (provoked by social isolation)

and cognitive dysfunctions (commonly known as ‘chemo-brain’) including:

  • Difficulty with concentration
  • Everyday memory loss
  • Difficulty retaining information
  • Poor Processing efficiency (i.e. slower responses)

So, is there a relationship between cognitive vulnerability and emotional vulnerability?

Crucially, Professor Derakshan divulged during her fascinating Science week talk that her team at Birkbeck have identified a directional causal relationship, in which cognitive dysfunction highly exaggerates the severity of psychological (or emotional) vulnerabilities (i.e. anxiety) experienced by breast cancer survivors. Furthermore, she stated the team extended their research to discover that this relationship is moderated by the grade of breast cancer diagnosed. For instance, women diagnosed with a higher grade (grade 3) of breast cancer exhibit a stronger relationship between cognitive vulnerability and emotional vulnerability.

Taking, all this novel research into consideration Derakshan raised an interesting point promulgating that it is imperative for future research to examine the cognitive health and emotional health of breast cancer survivors in unison, a previously problematic issue within the field of psycho-oncology.

How are researchers at Birkbeck aiming to build resilience to cognitive dysfunction and emotional vulnerability?

Neuroimaging research has shown structural and function changes in the brain related to the cognitive dysfunction(s) experienced following the completion of anti-cancer treatment, such cognitive dysfunction(s) is described by researchers as a ‘hidden cost’ of treatment as there are no significant behavioural differences observed when performance is compared with a control population. Interestingly, cognitive neuroscientists have evinced that breast cancer survivors recruit additional cognitive resources in order to compensate for the inefficiency (dysfunction) of their chemo-brain, this process is known as ‘compensatory effort’.

Furthermore, clinical research has reported that psycho-therapies such as cognitive behavioural therapy (CBT) are ineffective in adequately reducing the severity of emotional symptomologies encountered by the breast cancer population. Taken all this research into consideration, Derakshan and her Birkbeck laboratory in partnership with the BRiC centre are experimentally analysing the effect of exercising cognitive function through the use of neurocognitive interventions including, the Adaptive Dual N-back Training on emotional vulnerability—with promising results already being discovered.

One captivating study highlighting these incredible that was discussed by Derakshan during the talk, revealed that women that received 12-days of Adaptive Dual N-back training presented with significantly reduced levels of anxiety and distress, with these effects being sustained at the 14-18-month follow-up. Additionally, the study also showed a decrease in women’s rumination at the final follow-up, 14-18-months post-training. Derakshan disclosed that one possible explanation for these highly promising findings is that exercising cognitive function through adaptive training increased the fronto-parietal connectivity by enhancing the process of myelination and/or strengthened the synaptic connectivity.

In sum, Professor Derakhshan presented a highly insightful talk, outlining the incredible role that cognitive neuroscience has in promoting sustained cognitive and emotional resilience in women diagnosed with one of the most prevalent malignancies in the world.

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