Computational Genomics

Lead Research Organisation: MRC Laboratory of Molecular Biology

Abstract

The genome sequencing projects of organisms from various parts of the tree of life provide us with repertoires of genes for a large number of bacteria and animals. Many of these genes are of unknown function, including many of those genes that regulate other genes. We are interested in these regulatory genes, called transcription factors, and have developed a method for predicting their function (www.transcriptionfactor.org). We compare the repertoire of these regulators across different genomes, and experimentally study their role in defining the cell types of the immune system.In addition to regulatory interactions, we are also interested in the way that the gene products, proteins, interact with each other by binding to each other physically. To gain insight into this, we computationally analyse the three-dimensional coordinates of structures of protein complexes from x-ray crystallographic experiments. We have recently developed a database, www.3Dcomplex.org, to aid analysis of protein complexes.

Technical Summary

The wealth of genome sequence data that is accumulating for different species, such as the recent primate genomes, and also different individuals, for instance within the human population, provides us with an unprecedented opportunity for research into genome evolution. We are interested in general principles of genome evolution, as well as the evolution and dynamics of regulatory and physical interactions in organisms.|We study general principles of genome evolution in order to better understand the mode and tempo of genome evolution in different groups of species. We want to investigate whether there is a structure or grammar of genome evolution that confers properties such as evolvability and robustness on organisms. We also focus on particular groups of genes and proteins in genomes that regulate transcription and splicing by binding nucleic acids in a sequence-specific manner. For this purpose, we have developed two databases, transcriptionfactor.org and flytf.org. The transcription factor compendium provides the starting point for further computational and wet-lab experiments on differentiation of T cells in our group. Besides protein-nucleic acid regulatory interactions, we also do research on the evolution and dynamics of physical protein interactions. We approach this by drawing on protein complexes from proteomic data sets, as well complexes of known three-dimensional structure in the Protein DataBank.
 
Description BBSRC Case Studentship
Amount £91,932 (GBP)
Funding ID BB/1015914/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2012 
End 08/2015
 
Description EC Marie Curie Fellowship
Amount £180,895 (GBP)
Organisation Marie Sklodowska-Curie Actions 
Sector Charity/Non Profit
Country Global
Start 08/2011 
End 07/2013
 
Description EMBO Long-term fellowship
Amount £100,000 (GBP)
Organisation European Molecular Biology Organisation 
Sector Charity/Non Profit
Country Germany
Start 04/2010 
End 03/2012
 
Description EPSRC
Amount £260,679 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2011 
End 02/2014
 
Description ERC Starting Grant
Amount £1,000,000 (GBP)
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 01/2011 
End 12/2015
 
Description Fundacaó Para A Ciência & Tecnologia (FCT)
Amount £23,095 (GBP)
Organisation New University of Lisbon 
Department Foundation for Science and Technology
Sector Academic/University
Country Portugal
Start 05/2011 
End 05/2012
 
Description HFSP Long-term Fellowship
Amount £93,780 (GBP)
Organisation Human Frontier Science Program (HFSP) 
Sector Charity/Non Profit
Country France
Start 01/2011 
End 12/2013
 
Description King's College Cambridge Junior Research Fellowship
Amount £22,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 01/2009 
End 12/2009
 
Description Leverhulme Trust
Amount £14,620 (GBP)
Funding ID AIR-007 
Organisation The Leverhulme Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2011 
End 10/2012
 
Description Lister Institute
Amount £200,000 (GBP)
Organisation Lister Institute of Preventive Medicine 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2010 
End 09/2015
 
Description Lister Institute Summer Studensthip
Amount £2,000 (GBP)
Organisation Lister Institute of Preventive Medicine 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2012 
End 09/2012
 
Description MRC Capacity Building Studentship
Amount £36,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2007 
End 09/2011
 
Description MRC Training Fellowship in Biomedical Informations
Amount £75,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2006 
End 07/2009
 
Description Schroedinger Austrian Science Foundation Fellowship
Amount £54,000 (GBP)
Organisation Austrian Science Fund (FWF) 
Sector Academic/University
Country Austria
Start 10/2007 
End 10/2009
 
Description Thai Royal Government Scholarship
Amount £28,080 (GBP)
Organisation Government of Thailand 
Sector Public
Country Thailand
Start 10/2007 
End 09/2010
 
Description University of British Columbia Clinician Investigator Program
Amount £103,645 (GBP)
Organisation University of British Columbia 
Sector Academic/University
Country Canada
Start 10/2010 
End 09/2013
 
Description Wiener-Anspach Foundation (Cultural interactions between Oxford/Cambridge and Brussels)
Amount £27,000 (GBP)
Organisation Wiener-Anspach Foundation 
Sector Charity/Non Profit
Country Belgium
Start 01/2008 
End 12/2008
 
Title 3dcomplex 
Description A database for the quaternary structure of crystal structures: www.3dcomplex.org 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact This will allow scientists to access the correct quaternary structure of their protein of interest, as well as gain a better understanding through graphic visualization. 
URL http://www.3dcomplex.org
 
Title www.transcriptionfactor.org 
Description Databse for annotation of transcription factors based on DNA-binding domain assignments: www.transcriptionfactor.org 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact The database has allowed scientists to gain an overview of the repertoire of human transcription factors, as well as transcription factors of other model organisms (e.g. fly, flytf.org). 
URL http://www.transcriptionfactor.org
 
Description Folding & assembly 
Organisation University of Cambridge
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Data analysis as well as experiments carried out by a PhD student
Collaborator Contribution Experimental data on protein folding and assembly
Impact Publications: Han et al. (2007) Nat Rev Mol Cell Biol as outlined in publications
Start Year 2006
 
Description HaemAtlas 
Organisation NHS Blood and Transplant (NHSBT)
Country United Kingdom 
Sector Public 
PI Contribution Human-mouse conservation analysis
Collaborator Contribution Exposure to microarray data analysis of complete haematopoietic cell type data sets
Impact Publication: Watkins et al. (2009) Blood as outlined in publications
Start Year 2007
 
Description Haematopoietic stem cells 
Organisation University of Cambridge
Department Cambridge Institute for Medical Research (CIMR)
Country United Kingdom 
Sector Academic/University 
PI Contribution Data analysis of next generation sequencing data
Collaborator Contribution Exposure to transcription factor and epigenetic ChIP-seq data sets in haematopoietic cells.
Impact Publication Wilson et al. (2009) Blood as outlined in publications
Start Year 2008
 
Description Protein complex assembly 
Organisation University of Oxford
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution We computationally select targets which are particularly interesting for quaternary structure characterisation.
Collaborator Contribution Characterisation of protein quaternary structure by electrospray mass spectrometry
Impact Publication: Levy et al. (2008) Nature as outlined in publications
Start Year 2007
 
Description RIKEN 
Organisation RIKEN
Department The Functional Annotation of the Mammalian Genome (FANTOM) consortium
Country Japan 
Sector Public 
PI Contribution Transcription factor family annotation and analysis
Collaborator Contribution Exposure to large-scale human and mouse protein interaction data sets
Impact Publication: Ravasi et al. (2010) Cell as reported in the publications section.
Start Year 2006
 
Description Talks at conferences 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact I am invited to speak at on average about 10 international conferences a year, in addition to national conferences and seminars in departments. I accept invitations to one conference/seminar per month that requires travel outside the UK. This includes prestigious conferences such as Gordon conferences, Keystone conferences, CSHL/Wellcome Trust conferences and so forth.

I have not participated in any press conferences.
Year(s) Of Engagement Activity 2006,2007,2008,2009