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Dean's Prize awardee: Christine Schmidt

Christine Schmidt is an awardee of the Dean's Prize to help with her research into understanding how ubiquitylation pathways regulate the DNA damage response and associated processes.

The importance of these pathways is illustrated by the fact that a declining ubiquitin system and accumulating DNA damage can give rise to cancer and neurodegenerative diseases.

Christine's research will integrate cell biology, biochemical and quantitative microscopy/microarray techniques based on her previous experience.

She has previously completed postdoctoral positions in Professor Stephen Jackson's group at the Gurdon Institute/University of Cambridge between 2011 and 2016, and Dr Tom Misteli's group at the National Cancer Institute, National Institutes of Health, USA between 2009 and 2011.

Christine completed her PhD in Dr Frank Uhlmann's group at the CRUK London Research Institute/University College London between 2004 and 2009.

BBSRC David Phillips Fellowship

Since taking up The Dean's Prize, Christine has been awarded a prestigious five-year funded BBSRC David Phillips Fellowship to continue her research into ubiquitylation within and beyond the DNA damage response. Below is a summary of her fellowship project.

As we age, our cells become increasingly sensitive to accumulating damage in their genetic makeup, the DNA. Damage to DNA happens frequently, for instance, through radiation, sunlight, chemicals in tobacco smoke, and even from the oxygen in the air we breathe.

A rise in DNA damage is linked to some of the most severe and common problems that prevent us from healthy ageing. This includes cancer and diseases of the brain, such as loss of mental abilities.

In fact, certain permanent DNA changes that affect the ability of cells to repair DNA damage can lead to an early onset of these diseases and to premature ageing itself. With the global population ageing, the burden of age-related disorders will steadily increase.

It is therefore of urgent importance that we understand better how cells prevent DNA damage. This could lead to ways to prevent these disorders and thus contribute to healthy ageing across the lifespan.

To prevent permanent DNA damage, cells have found many different ways to repair damaged DNA. Hundreds of proteins - the workhorses of the cell - need to quickly change their behaviour in highly organised ways, an amazing feat that is far from being properly understood.

While cells can make use of an elaborate toolkit for this, the following way is especially fascinating: a little protein, known as ubiquitin, is attached to other proteins. Ubiquitin can be attached in different 'flavours', as a single ubiquitin or as poly-ubiquitin chains made up of many ubiquitins glued together in different ways. The process of ubiquitin attachment is called ubiquitylation.

Ubiquitylated proteins are recognised by other proteins, which triggers and allows the rapid change in the behaviour of the ubiquitylated proteins. Ubiquitylation relies on several enzyme groups, including ones known as E2s. We have recently found that several E2s play fundamental roles in repairing DNA damage.

One of the aims of the proposal is to better understand how precisely such E2s accomplish DNA repair. Another aim of the proposal is to analyse the proteins that recognise and translate different ubiquitin flavours to contribute to genome stability.

Together, this work will enhance our understanding of how different ubiquitylations change the behaviour of proteins in organised ways. Moreover, our studies could highlight the potential of selected E2s as drug targets, meaning that they could be changed by a medicine to give a desirable effect in the battle against age-related diseases, such as cancer.