Structural Biology and Bioinformatics - analyzing the human genome

Dr J. C. Whisstock

This year the first draft of the human genome will be completed, presenting a unique opportunity for understanding the molecular basis of disease. However, the quantity of data produced by the genome sequencing projects is unprecedented in biological science, hence new methods and approaches must be developed to glean meaningful results from this valuable resource. We have developed methods to rapidly analyse genomes and identify novel protein domains. In particular we are interested in identifying homologous domains that are present in extensively diverged organisms, for example, between yeast and human genomes. The primary objective of this project is to assign functions to these targets and test these predictions experimentally.

Project 1 - Identification of novel serpins in the human genome (Dr Whisstock, Dr Bottomley, Dr Bird & Dr Pike)

Several novel serine proteinase inhibitors (serpins) of unknown function have recently been sequenced. The primary objective of this project is to clone, express and purify these novel proteins and identify target proteinases.

Project 2 - Predicting the function of novel human proteins (Dr Whisstock, Dr Bird, Dr Pike, Dr Rossjohn & Dr Lesk)

A large number of proteins in the human genome are structurally and functionally uncharacterized. Bioinformatics techniques will be utilized to try to predict the function of a number of these proteins. These predictions will be tested by cloning and expressing interesting targets and performing relevant functional assays. Concurrently the project will also involve attempting to crystallize target proteins with a view to solving the structure via X-ray crystallography.