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Dr Karen Lipkow

Abstract:

Systems Biology of Chromosome Dynamics    Gene expression regulation is increasingly seen in the light of the 3D organisation of the entire genome[1]. A number of examples have shown that there indeed exists a deep functional relationship between gene expression and genome architecture, and a number of rare genetic diseases are caused by large scale mis-arrengement of the genome[2]. However, the physical mechanisms that shape the genome are still largely unknown.   

Chromosomes have a highly dynamic structure, which has been shown to change during changes in gene expression. Building on our experience with cellular architecture[3], we are now investigating the mechanisms of chromosome dynamics. We have identified several proteins that have the potential to actively influence the arrangements of chromosomes. The aim of this project is to determine to what extent structural changes preceed changes in gene expression.   

To this end, we are using quantitative fluorescent microscopy, microfluidics, bioinformatics, proteomics, chromatin conformation capture (Hi-C), gene expression analysis, and detailed computational modelling to investigate the interplay between structural proteins, genome architecture and gene regulation in the yeast S. cerevisiae. Several PhD projects are available, focusing either on experiments, computational analysis, or a combination of both. Please see http://lipkow.sysbiol.cam.ac.uk and contact Karen Lipkow to discuss further details.

References:

  1. Cavalli G, Misteli T. Functional implications of genome topology. Nat Struct Mol Biol 2013. 
  2. McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, et al. Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. Genome Res 2013. 
  3. Sewitz S, Lipkow K. Simulating bacterial chemotaxis at high spatio-temporal detail. Current Chemical Biology 2014 in press.