Case study: Chico Camargo
Chico’s first degree at São Paulo was in Molecular Sciences and very wide-ranging, covering maths, physics, chemistry, biology and computer science, so the first term of the CDT course was perhaps more familiar to him than to others. At São Paulo he completed a research project in the mathematical modelling of biological processes, which led to a six-month placement in Oxford with Professor Philip Maini at the Wolfson Institute of Mathematical Biology, which in turn led to his interest in the course at the Systems Biology CDT.
Chico particularly appreciates the fact that his degree gave him the ability to be either a biologist or a mathematician – and that the CDT’s first year built on this flexibility, giving him access to a whole range of different tools and a starting point in more or less any scientific discipline. Like other students, Chico found that the rotation projects in the first year changed his view of what he wanted to focus on in his DPhil. After a project in the group of Professor Ard Louis, a physicist based in the Rudolf Peierls Centre for Theoretical Physics, Chico realised that it was this area of research that most interested him.
Ard Louis’ group is interdisciplinary, and pursues research on the border between theoretical physics and chemistry, applied mathematics and biology, with a particular interest in biological physics. Chico’s DPhil focusses on the evolution of genotype-phenotype maps: in other words, the physical principles that underlie and sometimes constrain biological evolution, and determine which of all the many possible individual organisms (phenotypes) arise from the DNA ‘programming’ (genotypes). He describes himself as ‘a complex systems biologist building tools to predict evolution’.
The classical view of evolution states that random mutations take place in an organism’s DNA, which then allows natural selection to work, ‘choosing’ the organisms that are better adapted to their environment. Remarkably, the work of Ard Louis’ group and others has shown that the apparently ‘level playing field’ of mutations is far from level, and that evolution appears not to take any possible path.
Chico uses the analogy of Jorge Luis Borges’ story ‘The Library of Babel’, which contains all the possible books that can be written with a certain set of characters. Within this impossibly large library, there will nevertheless be many books that tell almost the same story – and it seems that the same may apply in nature. For example, using mathematical modelling, Ard Louis’ group has looked at all possible RNA strands of a given length and investigated what structures are adopted by most of them. Given how many different ways there are to fold up all these different RNA strands, it might be expected that there would be a very wide range of equally likely structures – but in fact the RNA shows a clear ‘preference’ for adopting some shapes. For RNA strands of a given number of bases, one of these preferred structures corresponds to the hammerhead ribozyme (a molecular catalyst). This means that natural selection is working within a biased set of options: some biological structures are just much more ‘designable’ than others.
Chico is fascinated by the fact that natural selection appears to work with structures and processes that are easy to find – or ‘robust to mutations’. He also sees the potential for extending his research on biological evolution to fields as varied as linguistics and machine learning, where the same kinds of bias may apply (for example, in relation to Chomsky’s theory of a ‘universal grammar’ hard-wired into the brains of every human being, no matter what their first language). Ultimately Chico hopes to stay in academia – though in what field is currently an open question.
‘I find science exciting because it always makes you a beginner. When you're dealing with the unknown, you have to stay humble, open and eager.’ – Chico Camargo