Comparative Genomics

Prof. Dr. Martijn Huynen  
CMBI
Tel. +31 24 3619543
E-mail: M.Huynen@cmbi.ru.nl

Introduction

The sequencing of complete genomes raises the question: how do we show that a genome is more than the sum of its genes ?, or, how do the proteins encoded in these genomes interact with each other to produce cells and phenotypes ? The core research focus of the Huynen group is to predict such functional interactions between proteins as there exist e.g. in metabolic pathways, signalling pathways or protein complexes.

On the one hand we develop computational genomics techniques that exploit the information in sequenced genomes and functional genomics data, like mRNA expression and protein-protein interactions, to make such predictions. Techniques that are used for this are sequence analysis tools for the prediction of homology and orthology, in combination with tools that combine the data for various sequenced genomes and functional genomics datasets with each other to make predictions about specific pathways. In this we collaborate with the computational biology department at the EMBL (Bork group).

On the other hand we make specific, testable predictions about pathways and the functions of proteins therein. For the latter we are directing our attention to systems that are relevant to the research at the RU/UMC, thus exploiting the possibilities there are for experimental testing of our predictions. As part of this we are presently using computational genomics to predict pathways and protein functions in the mitochondria. A specific example is a study on the likely interaction partners of frataxin. Frataxin is a well-known disease gene (Friedreich's ataxia) whose function has remained elusive despite more than six years of intensive experimental research. Using computational genomics we have shown that frataxin is likely involved in iron-sulfur cluster assembly in conjunction with the co-chaperone HscB/JAC1. We have also identified the complete eukaryotic protein set that has been derived from the alpha-proteobacteria, and that are mainly functioning in the mitochondria to predict pathways among these. Other examples include the prediction of a new protein interaction with Complex I (B17.2l), which was subsequently experimentally corroborated.

 We are also very much interested i n the evolution of the eukaryotic cell and in the origin and evolution of organelles like the mitochondria and the peroxisomes. The latter have often been hypothesized to be of "endosymbiotic" origin. However, based on our analyses they can be shown not to have an independent origin, but to have arisen fro the Endplasmic Reticulum.

Student projects

Biology, Molecular Life Sciences, Chemistry, Natural Sciences and Informatics students can do a research project at the CMBI. Some examples within the Computational Genomics group are described below.
Proteomics of mitochondria.
Prediction of protein interaction from genome data.

Team members

Martijn A. Huynen, group leader
Edwin Lasonder, staff
John van Dam, Postdoc
Bas E. Dutilh, Postdoc
Rasa Jurgelenaite, Postdoc
Shivakumar Keerthikumar, Postdoc
Richard Notebaart, Postdoc
Martin Oti, Postdoc
Sergio Rossell, Postdoc
Radek Szklarczyk, Postdoc
Isabel Duarte, PhD student
Philip Kensche, PhD student
Xiaowen Lu, PhD student
Fiona Nielsen, PhD student
Isiah Sama, PhD student

Former team members

Postdocs
Thijs Ettema
Juan Antonio Gabaldon Estevan
René van der Heijden
Urszula Kudla
Ludo Pagie
Joanna Parmley
Berend Snel

PhD students
Tim Hulsen
Vera van Noort
Jeroen van Reeuwijk
Guénola Ricard

Students
Lucas Brouwers, 2009
Luiz Canalle, 2003
Qian Cheng, 2010
Thomas Cuijpers, 2009
Evy van Damme, 2006
Ana Freitas, 2009
Ying He, 2007
Walter Hoolwerf, 2003
Leo Jacobs,  2006
Mark Jans, 2003
Gera Jellema
Maarten Kooyman, 2008
Sjoerd Paans, 2006
Daphne Rainey, 2003
Andreia Reis, 2009
Edouard Severing
Frank van Zimmeren, 2003