Regulatory Genomics and Systems Biology

NEWS & UPDATES

M. Madan Babu has been elected as a member of the European Molecular Biology Organisation (EMBO)

EMBO elects new members annually on the basis of scientific excellence and outstanding research contributions. The organisation promotes excellence in life sciences by supporting talented researchers, and stimulating exchange of scientific information. Madan, along with 57 other researchers, joins more than 1700 of the best researchers from Europe and around the world. Please see here for the EMBO and here for the LMB press release.

Discovering and understanding oncogenic gene fusions through data intensive computational approaches.

Although gene fusions have been recognized as important drivers of cancer for decades, our understanding of the prevalence and function of gene fusions has been revolutionized by the rise of next-generation sequencing, advances in bioinformatics theory and an increasing capacity for large-scale computational biology. The computational work on gene fusions has been vastly diverse, and the present state of the literature is fragmented. It will be fruitful to merge three camps of gene fusion bioinformatics that appear to rarely cross over: (i) data-intensive computational work characterizing the molecular biology of gene fusions; (ii) development research on fusion detection tools, candidate fusion prioritization algorithms and dedicated fusion databases and (iii) clinical research that seeks to either therapeutically target fusion transcripts and proteins or leverages advances in detection tools to perform large-scale surveys of gene fusion landscapes in specific cancer types. In this review, we unify these different-yet highly complementary and symbiotic-approaches with the view that increased synergy will catalyze advancements in gene fusion identification, characterization and significance evaluation. Paper by Natasha Latysheva and M. Madan Babu can be found here.

Welcome to Dr Mark Bayfield!

Dr Mark Bayfield is a sabbatical visitor from Dept of Biology, York University, Toronto and has joined our group for 5 months to learn techniques in computational biology (data integration and analysis of next generation sequencing data).

Affinity and competition for TBP are molecular determinants of gene expression noise

Cell-to-cell variation in gene expression levels (noise) generates phenotypic diversity and is an important phenomenon in evolution, development and disease. TATA-box binding protein (TBP) is an essential factor that is required at virtually every eukaryotic promoter to initiate transcription. While the presence of a TATA-box motif in the promoter has been strongly linked with noise, the molecular mechanism driving this relationship is less well understood. Through an integrated analysis of multiple large-scale data sets, computer simulation and experimental validation in yeast, we provide molecular insights into how noise arises as an emergent property of variable binding affinity of TBP for different promoter sequences, competition between interaction partners to bind the same surface on TBP (to either promote or disrupt transcription initiation) and variable residence times of TBP complexes at a promoter. These determinants may be fine-tuned under different conditions and during evolution to modulate eukaryotic gene expression noise. Paper by Charles Ravarani et al can be found here.

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