DrRobert Weinzierl

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.

Recently, we discovered a peptide sequence ("CompactionRegion 1" or "CR1"; UK patent granted May 2026; https://www.imperial.ac.uk/for-business/commercialisation/imperial-tech/technology-search/polypeptide-warhead-targeting-myc-for-cancer-therapy/) that binds to the intrinsically disordered N-terminal portion of MYC with high affinity and specificity. When expressed as a bioPROTAC, the CR1 peptide mediates destruction of >90% of highly overexpressed MYC in cancer cell lines. In human lymphoma cells (Raji cell line), expression of the CR1 bioPROTAC results in a rapid drop in the expression of MYC-responsive gene transcription (based on RNASeq data) and irreversible arrest of cell proliferation.