Dr Mark Hinds
Details
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Division: Structural Biology
Research Overview
The focus of my research is to gain an understanding of the molecular control of apoptosis. What are their 3D structures and how does this process work at the atomic level? Our approach to these questions has been by a combination of physical and biochemical techniques that includes cloning and protein expression, interaction kinetics, thermodynamics, and structure determination using Nuclear Magnetic Resonance (NMR).
Programmed cell death, or apoptosis, is a process that removes unwanted or damaged cells from an organism and is crucial for maintaining normal tissue homeostasis as well as playing a role in immune responses. Abnormal inhibition of apoptosis is a hallmark autoimmune diseases and of almost all cancers, whereas excessive cell death is implicated in many degenerative disorders.
Research Projects
- The Bcl-2 family
- The inhibitor of apoptosis family
- Caspase recruitment domains
Major Publications
- Hinds MG, Day CL. Regulation of apoptosis: uncovering the binding determinants. Curr Opin Struct Biol. 2005 Dec;15(6):690-9 PMID: 16263267 [PubMed - indexed for MEDLINE]
- Day CL, Chen L, Richardson SJ, Harrison PJ, Huang DC, Hinds MG. Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands. J Biol Chem. 2005 Feb 11;280(6):4738-44 PMID: 15550399 [PubMed - indexed for MEDLINE]
- Hinds MG, Lackmann M, Skea GL, Harrison PJ, Huang DC, Day CL. The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity. EMBO J. 2003 Apr 1;22(7):1497-507 PMID: 12660157 [PubMed - indexed for MEDLINE]
- Hinds MG, Norton RS, Vaux DL, Day CL. Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat. Nat Struct Biol. 1999 Jul;6(7):648-51 PMID: 10404221 [PubMed - indexed for MEDLINE]
- Day CL, Dupont C, Lackmann M, Vaux DL, Hinds MG. Solution structure and mutagenesis of the caspase recruitment domain (CARD) from Apaf-1. Cell Death Differ. 1999 Nov;6(11):1125-32 PMID: 10578182 [PubMed - indexed for MEDLINE]
- Day CL, Smits C, Fan FC, Lee EF, Fairlie WD, Hinds MG. Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1. J Mol Biol. 2008 Jul 25;380(5):958-71. PMID: 18589438 [PubMed - indexed for MEDLINE]
- Smits C, Czabotar PE, Hinds MG, Day CL. Structural plasticity underpins promiscuous binding of the prosurvival protein A1. Structure. 2008 May;16(5):818-29. PMID: 18462686 [PubMed - indexed for MEDLINE]
- Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, Fairlie WD, Hinds MG, Colman PM. Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22. PMID: 17389404 [PubMed - indexed for MEDLINE]