Supervisor: Dr Katerina Artavanis-Tsakonas
Division: Microbiology & Parasitology
Based at Department of Pathology, Tennis Court Road, Cambridge
Project title: Harnessing parasitic proteins to modulate skeletal muscle cells
Parasitic worms modulate host tissues through physical interactions and through secreting a mix of glycoproteins, glycolipids and polysaccharides. Trichinella spiralis, the only parasitic worm with a true intracellular stage, selectively infects striated muscle cells and, by secreting directly into the cell cytoplasm, modifies them to form a host-parasite ‘nurse cell’ complex. Since this interaction hinges on myotube reprogramming rather than destruction, exploring elements of T.spiralis nurse cell development provides an experimental paradigm for the remodeling and regeneration of skeletal myotubes. By expressing these proteins in muscle cell lines, we aim to characterize their effects through biochemical and cell biological approaches and assess whether these parasite elements can potentially be used to stabilize, transform and regenerate terminally differentiated cells.
Ubiquitin-dependent modification of skeletal muscle by the parasitic nematode, Trichinella spiralis. White RR, Ponsford AH, Weekes MP, Rodrigues R, Ascher DB, Mol M, Selkirk ME, Gygi SP, Sanderson CM, Artavanis-Tsakonas K.
PLoS Pathogens, in press.
How helminths use excretory secretory fractions to modulate dendritic cells.
White RR, Artavanis-Tsakonas K.
Virulence. 2012 Nov 15;3(7):668-77.
Characterisation of the Trichinella spiralis deubiquitinating enzyme, TsUCH37, an evolutionarily conserved proteasome interaction partner.
White RR, Miyata S, Papa E, Spooner E, Gounaris K, Selkirk ME, Artavanis-Tsakonas K.
PLoS Negl Trop Dis. 2011 Oct;5(10):e1340.
Stabilization of an unusual salt bridge in ubiquitin by the extra C-terminal domain of the proteasome-associated deubiquitinase UCH37 as a mechanism of its exo specificity. Morrow ME, Kim MI, Ronau JA, Sheedlo MJ, White RR, Chaney J, Paul LN, Lill MA, Artavanis-Tsakonas K, Das C.
Biochemistry. 2013 May 21;52(20):3564-78.
The tetraspanin CD82 is specifically recruited to fungal and bacterial phagosomes prior to acidification. Artavanis-Tsakonas K, Kasperkovitz PV, Papa E, Cardenas ML, Khan NS, Van der Veen AG, Ploegh HL, Vyas JM.
Infect Immun. 2011 Mar;79(3):1098-106.