Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

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Anaphase bridges in fission yeast cells
Whitby lab
Lactose permease represented using bending cylinders in Bendix software
Caroline Dahl, Sansom lab
Epithelial cells in C. elegans showing a seam cell that failed to undergo cytokinesis
Serena Ding, Woollard lab
Collage of Drosophila third instar larva optic lobe
Lu Yang, Davis lab
First year Biochemistry students at a practical class
Image showing the global movement of lipids in a model planar membrane
Matthieu Chavent, Sansom lab
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Department welcomes two new group leaders

The atrium of New Biochemistry

Two new group leaders, Drs Andrew Angel and Shabaz Mohammed, have joined the Department, complementing current expertise and interests.

Dr Angel is a Royal Society University Research Fellow and moves from the John Innes Centre in Norwich. He studied in Edinburgh as an undergraduate, gaining an MPhys in Mathematical Physics. Remaining there for his PhD, he worked on non-equilibrium statistical mechanics and networks in the group of Martin Evans.

He then spent a little over two years as a postdoc at Virginia Tech, continuing in the field of non-equilibrium statistical mechanics, working with Royce Zia and Beate Schmittmann.

On his return to Britain and the John Innes Centre, Dr Angel started to apply the techniques of physics and mathematics that he had learnt to biological problems. He worked jointly between the theory group of Martin Howard and the experimental group of Caroline Dean, studying vernalization - the acceleration of flowering by exposure to the cold of winter.

It is a particularly interesting system, Dr Angel says, as it is perhaps the best characterised example of a quantitative epigenetic response to an environmental signal.

‘We developed a model for epigenetic silencing in close collaboration with experimentalists at every step of the process. This led us to the conclusion that the quantitative memory must be held by the digital (on/off) silencing of a key gene in an increasing fraction of cells with increasing cold exposure.’

The conclusion was verified by experiment and published in Nature a few years ago.

Dr Andrew Angel

Dr Andrew Angel

His general interest, he says, is to focus on modelling the mechanisms underlying interesting biological phenomena. ‘Mathematical modelling allows one to postulate these mechanisms, which are often difficult to access directly by experiment, and make predictions concerning the broader behaviours resulting from them.’

At Oxford, he plans to take what he has learnt about applying simple mathematical models to biological processes and use it to study the regulation of genes by antisense transcription and the potential interaction of antisense transcription with chromatin. The work will be in collaboration with Professor Jane Mellor and her lab.

He believes that what he has learnt about epigenetic silencing could also synergise with researchers in the Department working on Polycomb and related systems.

Adding a mathematical perspective to biological problems can often be beneficial, he says. ‘Sometimes things are counter- or non-intuitive. Formulating the problem in terms of mathematics can rule out mechanisms that would otherwise have required time-consuming experiments to prove or suggest mechanisms that might otherwise not have been considered.’

Dr Shabaz Mohammed has been appointed as a University Senior Research Fellow in the Departments of Chemistry and Biochemistry. A chemist by training, he studied at UMIST (now the University of Manchester) and carried out work in the field of biological mass spectrometry for his PhD.

He followed this with a postdoc in the lab of Ole Jensen at Odense in Denmark where he worked on the development of technologies for studying post-translation modifications. He helped develop a method, now widely adopted, that allows quantitative analysis of phosphorylation and its role in cellular signalling.

In 2005, he moved to the lab of Albert Heck at Utrecht University, continuing in the field of proteomic technologies. He was made an Assistant Professor in 2008, starting his own group and remaining there until his move to Oxford.

Dr Mohammed hopes to build on his work in Utrecht where he successfully pursued two strands – the development of proteomic tools to address biological problems and the application of these tools. He will be trying to move this enabling technology forward so that it can be used to address some fundamental biological questions.

Dr Shabaz Mohammed

Dr Shabaz Mohammed

‘Up to now, the main questions in proteomics have been ‘what is the protein?’ and ‘how much is present?’’ he says. ‘Now, the context of the protein is important – so developing technology to look, for example, at phosphorylation, ubiquitination, methylation and acetylation, and using cross-linking to look at the interactions between proteins.’

A challenge is to refine the technology so that it can be applied on a large scale and the data integrated with other data such as RNA profiles coming from genetic studies. This requires the concomitant development of sophisticated informatics tools. One of the ultimate goals in the field is to build up a picture of how a simple organism, such as mycoplasma, works.

It is an exciting fast-moving area to be in, says Dr Mohammed. Studies that took weeks a few years ago can now be done in hours. The techniques that are currently being developed, although very labour intensive, will eventually filter into routine work.

In Oxford, Dr Mohammed will continue his work developing and using tools to measure post-translational modifications of proteins as well as exploring protein interactions. Both the Biochemistry and Chemistry departments are host to researchers studying a wide range of biological problems that lend themselves to these approaches.

Dr Mohammed has already established a collaboration with Francis Barr who is exploring the role of phosphorylase activities during mitosis. Other researchers he plans to work with in Biochemistry include Rob Klose and Kim Nasmyth. In Chemistry, the research programmes of Chris Schofield and Ben Davis have clear synergies with Dr Mohammed’s own interests.

Up to now, proteomics in Oxford has been run as a service with little time to develop the technology. Dr Mohammed’s appointment will help the field to evolve in new and exciting ways that will benefit researchers in Oxford and beyond.

The shared position gives him access to space in both departments. He will have proteomics equipment and wet lab space in the basement of the Biochemistry department, currently being kitted out, whilst his office will be based in Chemistry.

Dr Mohammed maintains a ‘guest’ lecturer status at Utrecht University and will continue to run a small group there as well.

 

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