Dr Jeff Babon
Division: Structural Biology
Maintenance of the blood system is largely controlled by the secretion of small glycoprotein messengers called cytokines. Cytokine exposure initiates an intracellular signalling cascade that is driven by activation of a family of receptor-bound tyrosine kinases known as JAKs (Janus Kinases). Under physiological conditions JAK activation and signalling is tightly regulated, in particular, by the SOCS (Suppressors of Cytokine Signalling) proteins.
However, in certain disease situations, mutant JAK overcomes its regulation by SOCS, leading to haematological malignancies. One example of this is the myeloproliferative disorders; a group of conditions that cause haematological cell types (platelets, white blood cells, and red blood cells) to grow abnormally in the bone marrow.
Our laboratory uses the techniques of Structural Biology, Biochemistry and Biophysics to uncover the mechanism of JAK/STAT signalling and its regulation by the SOCS proteins.
- Kuang Z, Lewis RS, Curtis JM, Zhan Y, Saunders BM, Babon JJ, Kolesnik TB, Low A, Masters SL, Willson TA, Kedzierski L, Yao S, Handman E, Norton RS, Nicholson SE. The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation. J Cell Biol. 2010 Jul 12;190(1):129-41. Epub 2010 Jul 5.PMID: 20603330
- Babon JJ, Sabo JK, Zhang JG, Nicola NA, Norton RS. The SOCS box encodes a hierarchy of affinities for Cullin5: implications for ubiquitin ligase formation and cytokine signalling suppression. J Mol Biol. 2009 Mar 20;387(1):162-74.PMID: 19385048
- Boyle K, Zhang JG, Nicholson SE, Trounson E, Babon JJ, McManus EJ, Nicola NA, Robb L. Deletion of the SOCS box of suppressor of cytokine signaling 3 (SOCS3) in embryonic stem cells reveals SOCS box-dependent regulation of JAK but not STAT phosphorylation. Cell Signal. 2009 Mar;21(3):394-404. Epub 2008 Nov 12.PMID: 19056487
- Babon JJ, Sabo JK, Soetopo A, Yao S, Bailey MF, Zhang JG, Nicola NA, Norton RS. The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase. J Mol Biol. 2008 Sep 12;381(4):928-40. Epub 2008 Jun 20.PMID: 18590740
- Babon JJ, McManus EJ, Yao S, DeSouza DP, Mielke LA, Sprigg NS, Willson TA, Hilton DJ, Nicola NA, Baca M, Nicholson SE, Norton RS. The structure of SOCS3 reveals the basis of the extended SH2 domain function and identifies an unstructured insertion that regulates stability. Mol Cell. 2006 Apr 21;22(2):205-16.PMID: 16630890
- Masters SL, Yao S, Willson TA, Zhang JG, Palmer KR, Smith BJ, Babon JJ, Nicola NA, Norton RS, Nicholson SE. The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues. Nat Struct Mol Biol. 2006 Jan;13(1):77-84. Epub 2005 Dec 20.PMID: 16369487
- Babon JJ, Yao S, DeSouza DP, Harrison CF, Fabri LJ, Liepinsh E, Scrofani SD, Baca M, Norton RS. Secondary structure assignment of mouse SOCS3 by NMR defines the domain boundaries and identifies an unstructured insertion in the SH2 domain. FEBS J. 2005 Dec;272(23):6120-30.PMID: 16302975
- Hands-Taylor KL, Martino L, Tata R, Babon JJ, Bui TT, Drake AF, Beavil RL, Pruijn GJ, Brown PR, Conte MR. Heterodimerization of the human RNase P/MRP subunits Rpp20 and Rpp25 is a prerequisite for interaction with the P3 arm of RNase MRP RNA. Nucleic Acids Res. 2010 Jul 1;38(12):4052-66. Epub 2010 Mar 9.PMID: 20215441
- Babon JJ, Morgan WD, Kelly G, Eccleston JF, Feeney J, Holder AA. Structural studies on Plasmodium vivax merozoite surface protein-1. Mol Biochem Parasitol. 2007 May;153(1):31-40. Epub 2007 Jan 30.PMID: 17343930
- Feng ZP, Keizer DW, Stevenson RA, Yao S, Babon JJ, Murphy VJ, Anders RF, Norton RS. Structure and inter-domain interactions of domain II from the blood-stage malarial protein, apical membrane antigen 1. J Mol Biol. 2005 Jul 22;350(4):641-56.PMID: 15964019
Current Laboratory Members
Faculty Member: Jeff Babon, BSc(Hons) PhD Melbourne
Senior Post-Doctoral Fellow: James Murphy, BSc(Hons) Canterbury, PhD ANU
Postgraduate student: Leila Varghese, BSc(Hons) Melbourne
Postgraduate student: Kelan Chen, BSc Melbourne (Joint with Molecular Medicine division)
Research technician: Tom Laktyushin, BSc(Hons) LaT
Research technician: Sam Young, BSc ANU, BMus(Hons) ANU