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Dr Joe Boyle

Research Interests

My current project aims to find a novel small molecule inhibitor for the innate immune receptor TLR4. I am taking an in silico approach by using target- and ligand-based virtual screens to find molecules which bind to the extracellular region of TLR4. High-scoring molecules will be assessed for their ability to inhibit NFkB activation through the TLR4 receptor in HEK293 cells and to inhibit cytokine production in RAW293 cells. Molecules with activity in the low micromolar range will be adapted in order to analyse their structure-activity relationship with the intention of producing potent TLR4 inhibitors. 

Other interests include structural analysis of the assembly of Caspase Recruitment Domain (CARD) complexes and phylogenetic analysis of the Nucleotide-Binding Oligomerisation Domain Receptor (NLR) family.

Keywords

virtual screen ; NLR ; TLR4 ; CARD

Key Publications

Trendelenburg AU1, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol. 2009 Jun;296(6):C1258-70.
Boyle JP1, Monie TP. Computational analysis predicts the Kaposi's sarcoma-associated herpesvirus tegument protein ORF63 to be alpha helical. Proteins. 2012 Aug;80(8):2063-70.
Mo J1, Boyle JP, Howard CB, Monie TP, Davis BK, Duncan JA. Pathogen sensing by nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is mediated by direct binding to muramyl dipeptide and ATP. J Biol Chem. 2012 Jun 29;287(27):23057-67.

Boyle JP1, Mayle S, Parkhouse R, Monie TP. Comparative Genomic and Sequence Analysis Provides Insight into the Molecular Functionality of NOD1 and NOD2. Front Immunol. 2013 Oct 7;4:317.