Deciphering the signalling functions of pseudokinases

Deciphering the signalling functions of pseudokinases

Project details

Despite exhibiting low to no catalytic activity, pseudokinases contribute to many human diseases, including cancers, when mutated or overexpressed.  This non-enzymatic sub-family controls cellular signalling using a host of “non-catalytic mechanisms” to integrate, orchestrate and efficiently activate kinase signalling pathways. However, how pseudokinases dynamically assemble and regulate oncogenic signalling pathways remains, in most cases, unclear.

We have a range of projects available that integrate cutting-edge technologies, such as structural biology, chemical biology, proteomics, high-throughput screening and  imaging to address this knowledge gap.

Each project will aim to resolve pivotal aspects of pseudokinase signalling and regulation, including kinase/pseudokinase signalling dynamics in vitro and in cells.

Students with an interest in biochemistry, chemical biology, drug synthesis, structural biology, imaging technologies and cancer biology are encouraged to apply.

About our research group

Our lab seeks to understand how the protein kinase family orchestrates complexed intracellular communication networks. We are particularly interested in acquiring a deep understanding at the molecular level of the catalysis-independent signalling functions of kinase/pseudokinase scaffold. We focus on identifying the mechanisms that lead to “out of control” signaling, a common cause of cancers and inflammatory disorders and use our basic research discoveries to develop novel therapeutic strategies to counteract kinase driven diseases (Patel, Structure 2016 24(9):1550; Patel, Nat. Commun. 2017 8(1):1157; Lucet, Methods Mol Bio 2017 1636:91)

We employ a multidisciplinary approach including kinase biochemistry and biology, structural biology (X-ray crystallography and cryo-EM), assay development, high-throughput screening, proteomics, imaging and chemical biology to gain high-resolution insights into kinase/pseudokinase signaling complexes.

Researchers:

Dr Onisha Patel
Dr
Onisha
Patel
ACRF Chemical Biology division
Dr Michael Roy
Dr
Michael
Roy
ACRF Chemical Biology division

Dr Kelly Rogers

Dr Kelly Rogers at a microscope
Dr
Kelly
Rogers
Division Head; Head, Centre for Dynamic Imaging

Project Type: