Structural Biology

The structural biology laboratory’s research program is aimed at understanding life processes at a molecular level. Our main focus is on the structure and function of proteins, in particular, those that act as molecular machines.
The group uses an array of techniques, especially:

  • X-ray crystallography,
  • Recombinant DNA technology,
  • Protein chemistry,
  • Biophysics and bioinformatics.

The laboratory has several themes including:

  • Membrane proteins,
  • Proteins that undergo dramatic structural changes,
  • Light harvesting proteins and molecular machines.

Current projects include: the CLIC chloride ion channels, RNPs, integron/gene cassette proteins, light-harvesting proteins, serpins, tumour suppressors, archaeal evolution and protein structural transitions.

CLIC ion channel

structural change of CLIC-1CLIC 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. CLIC proteins are unusual in that they exist in both globular and integral membrane states. The CLIC protiens are highly conserved in vertebrates with homologues in invertebrates. CLIC proteins can form chloride channels in vitro and in vivo.

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. We believe that this transition represents part of the functional cycle, as CLIC1 goes from a soluble form to a membrane bound form, prior to forming a channel.

Our current goal is to determine the structure of the integral membrane form of a CLIC protein.

Molecular chaperones.

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 immuno-modulatory protein.

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

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).

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.

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.

The structural biology laboratory’s research program is aimed at understanding life processes at a molecular level. Our main focus is on the structure and function of proteins, in particular, those that act as molecular machines.

The group uses an array of techniques, especially:

  • X-ray crystallography,
  • Recombinant DNA technology,
  • Protein chemistry,
  • Biophysics and bioinformatics.

The laboratory has several themes including:

  • Membrane proteins,
  • Proteins that undergo dramatic structural changes,
  • Light harvesting proteins and molecular machines.

Current projects include: the CLIC chloride ion channels, RNPs, integron/gene cassette proteins, light-harvesting proteins, serpins, tumour suppressors, archaeal evolution and protein structural transitions.