Network rewiring by cancer fusion gene. © MRC Lab of Molecular Biology, adapted by Paul Margiotta.

Network rewiring by cancer fusion gene. © MRC Lab of Molecular Biology, adapted by Paul Margiotta.

In today’s digital world, it is not surprising that computers are laying the groundwork for many biological and medical discoveries. The completion of the human genome project in 2003 allowed scientists to unravel the entire DNA sequence required to build a human. This was a huge scientific breakthrough with fantastic potential but also resulted in the production of daunting amounts of biological data, bringing with it the challenge of how to process and interpret it all.

One of the leaders at the forefront of computational biology is Dr Madan Babu Mohan. Dr Mohan and his team at the MRC Laboratory of Molecular Biology in Cambridge, UK are using computational approaches to analyse large biological datasets to understand more about regulatory processes in the body. Dr Mohan states that “machine learning and other data science approaches have the potential to revolutionise biology and medicine. With an ability to extract knowledge from large-scale datasets, we can discover complex patterns, make non-obvious connections and accelerate the process of discovery.” Dr Mohan remembers, when he first became interested in science, being particularly excited about the genomics revolution; realising the enormous potential this would have to reveal how an individual functions at a molecular level.

Imagine Victoria station at rush hour with thousands of commuters crossing paths and interacting. As a bystander this may appear to be complete chaos but to each commuter they are trying to get to a specific destination to carry out a specific task. This is similar to biological processes in the human body; each of the body’s thousands of proteins are on a mission to carry out their own unique function. Whilst we could study each individual protein in isolation (as you could follow an individual commuter to map their route), how can we start to understand the bigger picture? How do groups of proteins ‘know’ where to go and what other proteins they need to interact with in order to achieve their specific role within the body?

Dr Mohan is harnessing modern day computing power to try to understand the interactions of these proteins. The revolutionary aspect of Dr Mohan’s work is the ability to analyse large and complex amounts of scientific data, provide an overview and use it to strengthen our current understanding of cellular and protein function within a healthy body and the network of detrimental changes that occur during diseases such as cancer. (Akin to following the whole rail network rather than one single journey, we can understand where trains have come from, who drives them, and more about how they become delayed).

One particular aspect of Dr Mohan’s work focuses on studying how the different structures of proteins determine their function and interaction with other proteins. Previously, scientists believed that proteins need to adopt a rigid structure, and were only able to interact with other proteins complimentary in shape; in the same way that a puzzle piece can only be joined to another of a specific shape. However, the discovery of ‘unstructured’ proteins changed this view. Dr Mohan has found that these ‘unstructured’ proteins lack a rigid structure and are flexible in shape and therefore are able to interact with a large range of different proteins (think of a long flexible wire, or a piece of thread). ‘Unstructured’ proteins are now thought to be essential for life and therefore have become prime targets to help understand complex cellular interactions and causes of human diseases including neurodegeneration.

We are pleased to award the Francis Crick Medal and Lecture to Dr Mohan for his major and widespread contributions to computational biology. Join us on Wednesday 7 December to hear Dr Mohan give his prize lecture on ‘Unstructured proteins: cellular complexity and human diseases’.