Birkbeck students’ away day fuelled their appetite for interdisciplinary collaborative research

Last week a select group of Birkbeck’s BSc Biomedicine and MRes Global Infectious Diseases project students with a few others visited The Francis Crick Institute, informally known as ‘Sir Paul’s Cathedral’, located just a short walk from Birkbeck’s main campus.

The Crick Institute (formerly the UK Centre for Medical Research and Innovation) is a biomedical research centre right at the heart of London. The institute is named after Francis Crick, co-discoverer of the structure of DNA, who shared the 1962 Nobel Prize for Physiology and Medicine with James Watson and Maurice Wilkins.

La Young Jackson from International Students’ Administration team in collaboration with the Scientists from the Crick Institute organised this trip which was part of enhancing international students’ experience agenda at Birkbeck. The Birkbeck group was hosted and guided by Dr Minee Choi, a brilliant neuroscientist and researcher who showed the laboratory facilities and the sophisticated equipment used by the scientists working at the Crick.

Borna Matubber, a BSc Biomedicine Independent Research Project Student at Professor Sanjib Bhakta’s Mycobacteria Research Lab at Birkbeck, University of London said: “This was an amazing opportunity to interact with the scientists at the biggest single biomedical laboratory in Europe! It was truly motivating for young researchers like us to go above and beyond and appreciate how discoveries to change lives.”

Professor Bhakta adds: “A collaborative interdisciplinary approach is the way to address many of the major global challenges of our time. Students had the opportunity to step outside their lab and own zone of interest to think beyond the obvious, reflect and bring new energy back to their project. This would add great value to their research experience that we always encourage at our institution.” Professor Bhakta added.

Birkbeck officially partners with the Crick, UCL and LSHTM to jointly host the World TB Day 2020 on the 24 March at UCL Great Ormond Street Institute of Child Health.

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Me, Human: ‘The Big Discussion’

Dr Gillian Forrester presented ‘Me, Human: The Big Discussion’ at London’s Science Museum, where an expert panel reflected on questions of developmental psychology.

The event was held in the Hans Rousing Lecture Theatre and began with an introduction to the Me, Human project, a set of live experiments currently being held at Live Science at the museum. Dr Forrester demonstrated evolution through a set of handmade puppets that are on display in the Me, Human gallery and then went on to introduce her esteemed panel which included Professor Uta Frith, a developmental psychologist, Professor Ben Garrod, an evolutionary biologist, primatologist and broadcaster, and Tony King, an independent researcher with the Aspinall Foundation.

 

In her introduction, Dr Forrester noted both the number and the diversity and of attendees, the Science Museum had welcomed over the course of the project, which will yield a rich source of data to be released in the coming months. The Me, Human experiments include a number of stations which investigate how different sides of our brains are involved in various functions in our day-to-day lives. Earlier that day attendees of the discussion were invited to attend the Me, Human gallery and take part in these experiments in order to understand whether they are dominant in their left or right brain.

The Me, Human team and evolution puppets

The conversation was informal with comments and questions welcomed throughout the discussion. Dr Forrester started the discussion with a question on developmental psychology, which was followed up with a question from a member of the audience who asked simply, “What’s next for us in terms of evolution?” – something the panel said was hard to predict! The panel highlighted the importance of experiments like the Me, Human project and the need for human and animal behavioural psychology to be researched in tandem as Professor Garrod exclaimed: “We are animals!”  Other questions posed to the panel included; what’s next for humans? How does social media impact our need to be social in a time where we are increasingly connecting to others through technology?

Later in the panel, Dr Forrester questioned Professor Frith on her theory of ‘slow science’ – her belief that academics should only publish once a year to ensure a quality over quantity approach to research in order to sustain the practice.

It is clear that the Me, Human project has garnered invaluable results and it was positive to see a mix of academics and the general public in the audience. During the conversation, Professor Garrod asked how many of the audience are researchers and not, and highlighted the need for the non-researchers in the continuation of the field of psychology.

The Me, Human project be at the Science Museum London until 30 September 2019.

 

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Antibiotic resistance: a challenge to rival climate change

Dr Clare Sansom, Senior Associate Lecturer in Birkbeck’s Department of Biological Sciences reports on a recent, international capacity-building workshop to tackle antimicrobial resistance and accelerate new antibiotic discovery, sponsored by the global challenges research fund (GCRF). 

Credit: Mr Harish Patel

Antibiotic resistance is one of the most serious threats to global health: some commentators have even rated it as important as climate change. It is, however, one that the research community – particularly in the academic and not-for-profit sectors – is finally investing serious resources in tackling. Research into novel antibiotic targets and the compounds that can interact with them is burgeoning throughout the world. At Birkbeck, research in the ISMB-Microbiology Research Unit, headed by Professor Sanjib Bhakta focuses on tackling antibiotic resistance in priority bacterial pathogens, the causative agent of a number of global infectious diseases.

In July 2019 Prof Bhakta invited his collaborators in the UK and overseas to a workshop at Birkbeck to discuss ways of tackling drug resistance. This was funded through the UK’s Grand Challenges Research Fund (GCRF), an initiative to promote the welfare of developing countries through international research. Delegates were welcomed by Birkbeck’s Pro-Vice-Master for internationalism, Professor Kevin Ibeh, and then heard brief presentations from Dr Sarah Lee on the place of the GCRF in Birkbeck’s research portfolio and Dr Ana Antunes-Martins on the mission of the neighbouring London International Development Centre. This combines the resources of seven University of London institutions in the Bloomsbury area, including Birkbeck, to support interdisciplinary research, capacity building and public engagement for international development.

In an intense scientific session, the first researcher to speak was Professor Nicholas Keep, Executive Dean of the School of Science at Birkbeck and a structural biologist. He presented some structures of Mycobacterium tuberculosis proteins known or believed to be novel prospective therapeutic targets that had been solved at Birkbeck or UCL using the three main techniques of structural biology: X-ray crystallography, nuclear magnetic resonance (NMR) and electron microscopy (EM). These included a small enzyme called resuscitation-promoting factor, which is necessary for the bacteria to emerge from their dormant state, and a rather larger one that synthesises an important component of the cell wall. This work is enabled by excellent local facilities including a new Titan Krios microscope in Professor Helen Saibil’s EM lab, and even more powerful national and international ones.

Beta-lactamase enzymes, which inactivate drugs in the penicillin family, are one of the most common antibiotic resistance mechanisms, but they are not as well understood in mycobacteria as they are in some other human pathogens. Prof Anindya S. Ghosh from the Indian Institute of technology in Kharagpur – incidentally, the speaker who had travelled the furthest – described his group’s work in collaboration with Prof Bhakta and Prof Tabor’s lab (funded by a Newton-Bhabha international fellowship to Sarmistha Biswal at Birkbeck this year) in designing inhibitors for beta-lactamases and other proteins that interact with penicillins and prevent their antibiotic action. He set out several more opportunities for collaborative research, including finding molecules that prevent the formation of drug-resistant microbial biofilms.

The next two speakers came from continental Europe, and both described novel natural sources of potential anti-infective drugs. Prof Franz Bucar from the University of Graz, Austria focused on drugs from plant and fungal sources, including an intriguingly named flavonoid, skullcapflavone II (derived from the poisonous skullcap mushroom). This and other recently discovered natural products were also highlighted on a poster by Prof Bucar’s doctoral student, Julie Solnier.  Prof Ester Boix from Universitat Autònoma de Barcelona in Spain described how the antimicrobial peptides that we synthesise as a defence against bacteria might be harnessed as drugs. Her group has used the HT-SPOTi assay developed in Prof Bhakta’s group at Birkbeck to screen human ribonuclease peptides against macrophages infected with Mycobacterium tuberculosis.

Dr Jody Phelan and Prof Taane Clark from the London School of Hygiene and Tropical Medicine asked – and answered – the question ‘What can the M. tuberculosis genome tell us about drug resistance in TB?” This bacterial genome contains over 4 million base pairs of DNA and about 4,000 genes, compared to the 3.3 billion base pairs and 20,000 genes of the human genome. Resistance to any of the over 10 drugs currently used to treat the disease arises largely when treatment is irregular or stopped too soon, and the genetic changes responsible for each type of resistance can be identified rapidly using whole genome sequencing. It is now possible to use this in clinical practice to predict which drugs a given strain is most likely to be resistant to, and thence to recommend a personalised course of treatment for an individual patient.

Dr Simon Waddell from the University of Sussex in Brighton described how the RNA molecules transcribed from the M. tuberculosis genome change during the lifecycle and with the environment of the bacterium, and how this analysis, known as transcriptomics or RNA profiling, can both track and predict responses to drug therapy. One new compound, a benzothiazinone discovered through a high-throughput screen, was found to induce transcription from the same set of genes as cell-wall synthesis inhibitors, suggesting that it is likely to act against the bacterium through the same or a similar mechanism.

These two ‘omics talks were followed by two extremely short ones by scientists based in the Department of Chemistry at University College London. Dr Rachael Dickman (from Prof Alethea Tabor’s lab in UCL) is developing potential antibacterial agents based on a complex amino acid, lanthionine. These ‘lantibiotics’ bind to Lipid II, which is formed during cell wall synthesis, and therefore act as inhibitors of that synthesis. Professor Helen Hailes described the antimicrobial properties of a series of isoquinolines that selectively inhibit slow-growing mycobacteria and that may also potentiate the activity of other drugs by preventing their efflux from bacterial cells.

With the last talk, by Prof Matthew Todd of the UCL School of Pharmacy, the workshop moved from pure science to begin to discuss the economics of drug discovery. Prof Todd’s open source drug discovery work, which began with a project on malaria, is completely open: all the data is freely available, all ideas are shared, no results are ‘owned’ by any of the researchers and there will be no patents. It is a timely approach and one that can involve anyone – Prof Todd has recently been awarded a grant by the Royal Society to work with teenagers at Sevenoaks School to develop new antifungals – and one that might, perhaps, help any of the academic groups represented at the workshop turn their novel ideas into drugs that are useful against the killer disease.

The final networking session was accompanied by an engaging talk by me, Dr Clare Sansom, about the important issue of communicating the challenge of antimicrobial resistance to non-scientists. This was illustrated with frightening scenes from fictional accounts of possible post-antibiotic futures and included a quiz that many of the experts present found surprisingly challenging. This workshop was organised in collaboration with the Commonwealth Scholarships Commission, UK and approved by the Royal Society of Biology for continual professional development credit.

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Science Week 2019: engineering a dinosaur

Dr Clare Sansom, Senior Associate Lecturer in Birkbeck’s Department of Biological Sciences reports on the 2019 Rosalind Franklin Memorial Lecture, delivered by Professor Emily Rayfield on how computational tools are reshaping our understanding of form and function in fossil animals.

Since 2016, the School of Science at Birkbeck has held an annual lecture named for one of its most distinguished alumni, Rosalind Franklin. This lecture, which is always given by a notable woman scientist, forms part of the school’s Athena SWAN programme. Each Rosalind Franklin lecturer’s research field is closely aligned to one of the three departments that make up the School, Biological Sciences, Earth and Planetary Sciences, and Psychological Sciences. This was the year of the earth sciences, and the lecturer, Emily Rayfield, was a professor of paleobiology at the University of Bristol. She gave an engaging talk about how computer modelling is helping us understand the biology and behaviour of fossil animals, beginning with the dinosaurs.

Emily drew a contrast between the techniques used to study living animals and prehistoric ones. With living animals, there is a chance, at least, that we will be able to observe their behaviour, but with prehistoric ones all we have to go on is the fossils they leave behind. So how can we approach a question such as, what – and how – did dinosaurs eat? We can begin to understand this problem by relating the skulls, and particularly the jawbones, of living animals to their diets. Plotting the measured bite force of reptiles’ jaws, including those of the closest living relatives of dinosaurs, the crocodiles and alligators, against the size of those jaws, and then scaling up to the size of dinosaur jaw bones has suggested that the largest would have had a bite force of over 10 tonnes.

It is possible to get some idea of what fossil animals ate by, literally, looking at their dung. Fossilised faeces, or coprolites, are frequently found, and geologists can estimate the size of the creatures that produced them, as well as finding clues to their diets. The largest that have been seen are likely to have come from Tyrannosaurus rex. This monster, one of the largest land-dwelling carnivores that ever lived, measured over 40’ from nose to tail and stood about 12’ tall at the hips. Skeletal fragments found in dinosaur coprolites include those from some of the first birds. Fossilised bite marks and teeth, which differ in shape and size between herbivorous and carnivorous animals, can also fill gaps in the picture of dinosaur diets.

Feeding is only one aspect of animal behaviour, although an important one. Emily opened out her question to ask what the shape of an extinct animal’s bones can tell scientists about its behaviour more generally. Bones all respond to externally applied forces of stress (load per unit area) and strain (stretch per unit length). Wolff’s Law, which dates from 1892, states that any change in the function of bones, and therefore in the stresses and strains that they are exposed to, is directly followed by changes in their shape. In human terms, if an individual overloads his or her bones by, for example, taking up a strenuous sport, the bones will gain mass, whereas disuse will cause bone loss in astronauts exposed to low gravity as well as the chronically sick.  Mechanical loads experienced in utero affect the shape of the developing embryo and, going back to the example of feeding, animals that experience different diets develop different-shaped jaws. This can be observed in individuals of the same species, with mice raised on only soft food developing less efficient jaws than those raised on hard pellets. It is also reflected in species differences in both living and extinct animals: animals and their environments may have changed dramatically since ‘deep time’, but the laws of physics – and the basic structure of the cells and tissues they operate on – have not.

It is, of course, impossible to measure the stresses and strains that a dinosaur bone will have been subjected to, but it is not impossible to deduce them. This is where computers come in, via a mathematical technique known as finite element analysis.  In this, a complex structure is broken down into a number of simple shapes. A force is applied to each element and a computer program is used to estimate how it moves and changes shape.

To apply this technique to a fossil, you need to start with a digital model of that fossil, and this can now be done quite easily using a CAT scanner similar to those used in medicine. The model is then completed by adding any bones missing from that specimen. The model is combined with information from living relatives to estimate the stresses and strains on the bones.

Professor Emily Rayfield

Armed with all this data on the forms of, and loads experienced by, dinosaur skulls, it is possible to ask complex questions about their mechanics and evolution. It is now quite well known that modern birds evolved from a group of dinosaurs, and this begs the question of how they evolved their characteristic, but extremely diverse, beaks. Some herbivorous dinosaurs in the group known as the theropods (three-toed) had beaks and comparing models of similar sized dinosaur skulls with and without beaks has suggested that a beak reduced stress and strain during feeding. Large theropods were found to have experienced proportionally lower stress during feeding than smaller ones, with the exception of Spinosaurus, which had much higher stress than expected for its size.

At the end of the lecture, Emily moved on from the largest land-based fossils to look at some of the smallest: a group of primitive shrew-like mammals known as the ‘Jurassic fissure mammals’ that lived in crevices between rocks some 200 million years ago. Working with Pamela Gill, an expert on the anatomy of these creatures, Emily examined the fossilised jaws and teeth of two species and predicted differences in the speed and strength of their bites. Comparing patterns of wear on the teeth of these mammals with modern bats suggested a similar range of insect diets. This implies that, even at the very beginning of the mammalian radiation, species that occupied similar niches were beginning to diversify their diets; and it provides another example of how studies of the mechanics of fossil bones can lead to insights into the lives of animals from hundreds of millions of years ago.

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