Summary
Dr. Weinzierl's research focuses on the structure and function of gene-specific transcription factors (GSTFs) acting as human oncoproteins. Oncoproteins are proteins that fulfill important regulatory functions in the cell and are either mutated or dysregulated in cancer cells. Many of these also play key roles in normal ageing (senescence) processes.
One of the most important oncoproteins - responsible for around 2/3 of all human cancers - is the oncoprotein c-MYC (or ‘MYC’ for short). Most of the functionally active parts of MYC are intrinsically disordered and cannot form the defined and stable three-dimensional structure that many other folded proteins display. The laboratory thus focuses extensively on computational simulations of the structural ensembles of such intrinsically disordered proteins (IDPs) to gain new, experimentally verifiable insights into structure/function relationships of MYC. The laboratory is also pioneering high-throughput robotic approaches to identify the locations of transcriptional activation domains and regions involved in protein-protein interactions in IDPs.
Such studies will provide new insights into the central role of oncoprotein GSTFs in normal and pathological cellular conditions.
Selected Publications
Journal Articles
Tan L, Wiesler S, Trzaska D, et al., 2008, Bridge helix and trigger loop perturbations generate superactive RNA polymerases, Journal of Biology, Vol:7, ISSN:1475-4924
Nottebaum S, Tan L, Dominika T, et al., 2007, The RNA polymerase factory: a robotic in vitro assembly platform for high-throughput production of recombinant protein complexes., Nucleic Acids Research
Werner F, Weinzierl ROJ, 2002, A recombinant RNA polymerase II-like enzyme capable of promoter-specific transcription, Molecular Cell, Vol:10, ISSN:1097-2765, Pages:635-646
Books
Weinzierl ROJ, 1999, Mechanisms of Gene Expression, London, Imperial College Press, ISBN:9781860941269