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Professor Vassilis Koronakis

Abstract:

Remodelling of the mammalian host cell cytoskeleton by the WAVE regulatory complex. The WAVE regulatory complex (WRC) nanomachine drives formation of newly polymerised actin filaments at the mammalian cell plasma membrane to generate lamellipodia and membrane ruffles that are pivotal to cell processes (e.g. movement, phagocytosis) and pathology (e.g. cancer). The WRC is also crucial to host cell invasion by bacterial pathogens. How WRC is regulated in the cell remains unclear.  Our laboratory has identified a novel cellular activator of the WRC known as Arf GTPase that cooperates with Rac1 GTPase to control WRC(1). We uncovered that bacterial pathogens target this pathway through pathogen and host guanine nucleotide exchange factors (GEFs) that activate Arf and Rac1 to remodel the actin cytoskeleton via WRC and drive invasion into host cells(2, 3). Multiple parallel projects in the laboratory are investigating the biochemistry and cell biology of WRC activation and actin filament assembly via small GTPases (i.e. Arf, Rac1). You will work alongside PhDs and postdocs within the group to gain new insight into the function and control of WRC.

References:

  1. Koronakis V, Hume PJ,Humphreys D, et al. (2011). Proc Natl Acad Sci U S A.  
  2. Humphreys D, Davidson A, Hume PJ, & Koronakis V (2012). Cell Host Microbe 11(2):129-139. 
  3. Humphreys D, Davidson AC, Hume PJ, Makin LE, & Koronakis V (2013). Proc Natl Acad Sci U S A 110(42):16880-1688

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