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Department of Biochemistry

 
Darerca Owen

Small G protein-regulated signalling networks.

 

Small G proteins of the Ras superfamily are essential components to almost all processes of cell biology and since they were discovered their structures and functions have been intensively studied. They control an intricate network of intracellular signalling pathways and, not surprisingly, are found deregulated in many disease states, not least in cancer.

The Owen Group works mainly on members of the Ras and Rho families of small GTPases and wants to understand the complex interconnected networks these proteins control at a molecular level. It is only with a full understanding of these systems that we will be able to develop truly safe and effective drugs.

Activated Cdc42-associated kinase (ACK) is a non-receptor tyrosine kinase and an effector protein for the Rho family GTPase Cdc42. A substantial body of evidence has accumulated in the past few years heavily implicating ACK as a driver of oncogenic processes. A major objective for us is to delineate the complete Cdc42-ACK signalling system and determine its contribution to disease states.​

 

Research objectives

  • What is the signalling network controlled by the Cdc42 effector protein ACK.

  • Is the Cdc42-ACK signalling axis a therapeutic target?

  • Can peptide biologics be utilised as therapeutics towards Ras-driven cancers?

  • What drives the specificity of small G protein-effector complex interactions?

 

Key publications

Tetley GJN, Murphy NP, Bonetto S, Ivanova-Berndt G, Revell J, Mott HR, Cooley RN, Owen D (2020). The discovery and maturation of peptide biologics targeting the small G protein Cdc42: A bioblockade for Ras-driven signalling. J. Biol. Chem., doi: 10.1074/jbc.RA119.010077

Fox M, Crafter C, Owen D (2019). The non-receptor tyrosine kinase ACK: Regulatory mechanisms, signalling pathways and opportunities for attACKing cancer. Biochem. Soc. Trans., 47(6):1715-1731. doi: 10.1042/BST20190176

Tetley GJN, Szeto A, Fountain AJ, Mott HR, Owen D (2018). Bond swapping from a charge cloud allows flexible coordination of upstream signals through WASP: Multiple regulatory roles for the WASP basic region. J. Biol. Chem., 293(39):15136-15151. doi: 10.1074/jbc.RA118.003290

Tetley GJN, Mott HR, Cooley RN, Owen D (2017). A dock and coalesce mechanism driven by hydrophobic interactions governs Cdc42 binding with its effector protein ACK. J. Biol. Chem., 292(27):11361-11373. doi: 10.1074/jbc.M117.789883

Contact details

Research Group Leader  Darerca Owen

Email  do202@cam.ac.uk

Location  Sanger Building

Opportunities

The Owen Group is accepting enquiries from prospective postgraduate students.