Research Interests

Structural transition in CLIC1. A soluble monomer CLIC1 structure compared to B the half dimer structure observed after oxidation.	CLIC proteins are unusual in that they exist in both globular and integral membrane states.  The  CLICs are highly conserved in vertebrates with homologues in  invertebrates.  CLICs can form  anion channels (chloride) in vitro and in vivo.  Our goal is to gain a comprehensive understanding of the CLIC proteins in collaboration with Sam Breit, St Vincent's Hospital, Sydney, Michele Mazzanti, University of Rome "La Sapienza" and Louise Brown, Macquarie University. We have determined several crystal structures of CLIC proteins in the soluble form.  In addition, we have discovered a dramatic structural change in CLIC1 which is stabilised by oxidation.  Our current goal is to determine the structure of the integral membrane form of a CLIC protein. more information on CLIC proteins
	Membrane proteins.  Membrane proteins are the conduits through which cells and cellular organelles communicate with their environments.  more information on Membrane Proteins
Cpn10	Molecular chaperones.  Protein folding is a key biological problem.  The environment in the cell is crowded and the conditions not necessarily conducive to spontaneous folding.  Several families of proteins are involved in assisting proteins to fold correctly or preventing aggregation and inappropriate interactions.  These proteins are known as molecular chaperones.  We are focusing on several types of molecular chaperone, including the chaperonin, Cpn10.  Cpn10 also acts as an immunomodulatory protein and we are studying its structure in collaboration with CBio Ltd Biopharmaceuticals, Steve Mahler, UNSW and Chris Marquis, UNSW.
PE545 Crystal PE545 structure	Cryptophyte light harvesting proteins.  Cryptophytes are an unusual type of single-celled algae that have resulted from the endosymbiosis of a red algal cell inside a eukaryotic host.  Like cyanobacteria and red algae, the cryptophytes have preserved a light harvesting system based on phycobiliproteins that are members of the globin fold superfamily.  Unlike cyanobacteria and red algae, the cryptophyte phycobiliproteins are soluble and reside in the lumen on the thylakoid.  We are using crystallography to unravel the mechanism by which these proteins trap light photons and transfer the energy to the membrane bound photosystem.  We are collaborating with Greg Scholes, University of Toronto who's group is probing the light harvesting system via ultrafast laser spectroscopy. Our crystals of the light harvesting proteins diffract to ultra high resolution (<1Å). more information on Light Harvesting Proteins
Bal32a, an environmental integron/gene cassette protein	Integron/gene cassette proteins. Lateral Gene transfer is a major phenomenon in bacteria and archaea.  The integron/gene cassette system interconnects bacterial communities via a metagenome of cassette encoded genes which can be acquired, rearranged and discarded as a result of environmental pressure.  The integron/gene cassette system is the major mechanism by which pathogens gain antibiotic resistance.  Most of the proteins encoded by the gene cassettes are unrelated to proteins in the databases.  We are exploring the function of these cassette proteins from environmental samples as well as Vibrio, where many species contain large cassette arrays (>100 genes). This is a collaboration with Bridget Mabbutt, Macquarie University and Hatch Stokes, Macquarie University.  more information about Integron/gene cassette proteins
	Archaea and cold adaptation.  Most of the biosphere (>80%) is cold (permanently below 5°C), thus, a large proportion of organisms have evolved to thrive in cold environments. We are collaborating with Rick Cavicchioli, UNSW, who has established a comprehensive program to determine the mechanisms by which archaea adapt to cold environments.  We are looking at factors that allow proteins to function at low temperature as well as molecular chaperones and protein folding in psychrophiles.
Archaeal Lsm Yeast SmF	RNPs.  Ribonucleoprotein complexes form some of the most ancient, central machines in extant organisms.  The Sm/Lsm proteins from a core ring structure that appears in many RNPs in all three domains of life.  In collaboration with Bridget Mabbutt, Macquarie University, we are using x-ray crystallography to gain a better understanding of these ring complexes in both archaea and eukarya.
Shearing in antiparallel beta sheet	The b-sheet. We have analysed the physical interactions that affect the correlations of amino acids within beta sheets and beta ribbons. We have also identified the physical mechanism responsible for the shear and twist of beta structures in proteins.

Human Plasminogen Activator Inhibitor 2 (PAI-2). PAI-2 is a serpin that finds, binds to and inhibits Human Plasminogen. During the process of inhibition, the serpin undergoes an incredible conformational change, which involves inserting a loop into a beta sheet as an extra strand. We have determined the crystal structure of PAI-2 in the stressed state (image, PDB entry: 1BY7).

Rubisco. Rubisco is the most abundant protein in plants. Based on the structure, we have postulated a mechanism for closing and a mechanism for catalysis. (image, PDB entry: 1EJ7).

Updated Aug 2006