Projects for prospective PhD students

1. Coupling the cell cortex to membranes: structural basis for the activation and control of ezrin

Cells are dynamic: they change shape, communicate with each other and import/export signalling molecules. These dynamic processes are controlled via the interaction of the cell membrane with the underlying actin cytoskeleton and they are important for health, for example, they are critical for proper immune cell function. The goal of this project is to unravel the control of membrane dynamics by defining the interactions between the cell membrane and the proteins: ezrin and RhoA.

The structure, activation and function of ezrin and RhoA are being pursued via a combination of structural biology (X-ray crystallography, small-angle X-ray scattering and neutron scattering) and single molecule fluorescence microscopy (collaboration with Dr Till Böcking, UNSW).  By combining the results of these complementary approaches, we aim to understand how ezrin couples cortical actin filaments to membranes.  We are exploring the role of other proteins in this system, including the CLIC proteins.

Reference:

Jiang L, Phang JM, Yu J, Harrop SJ, Sokolova AV, Duff AP, Wilk KE, Alkhamici H, Breit SN, Valenzuela SM, Brown LJ, and Curmi PM (2014) CLIC proteins, ezrin, radixin, moesin and the coupling of membranes to the actin cytoskeleton: A smoking gun? Biochimica et biophysica acta 1838, 643-657. [PubMed link].

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2. Biological quantum control: How does protein structure control quantum optical properties in algal photosynthetic light harvesting systems?

The strange phenomena of quantum mechanics were not expected to play a direct role in life. However, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. Our aim is to relate protein structure to the emergence of quantum effects in the light harvesting proteins of marine algae. Understanding the link between structure and quantum effects will improve our knowledge of how nature achieves its remarkable efficiency in utilising the energy from the sun. This is likely to foster new technologies that improve the efficiency of solar energy systems.

We have discovered that cryptophyte algae have evolved a set of unique light harvesting proteins. Recently, we have shown that some of these organisms can switch between two forms of light harvesting system, where the insertion of a single amino acid appears to control a dramatic structural reorganisation of the protein. This switch potentially controls the utilisation of quantum effects in light harvesting.

This project will focus on determining the mechanisms that control the type of light harvesting protein produced by a particular organism. The structural basis for the switch will be determined via protein crystallography. The consequences of structural changes on the light harvesting capabilities of the proteins will be determined in collaboration with Prof. Greg Scholes (University of Toronto, Canada) and Dr. Jeff Davis (Swinburne University of Technology, Australia).

Reference:

Collini E, Wong CY, Wilk KE, Curmi PM, Brumer P, and Scholes GD (2010) Coherently wired light-harvesting in photosynthetic marine algae at ambient temperature. Nature 463, 644-647. [PubMed link].

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3. Synthetic biology: building an artificial molecular motor using protein modules

Molecular motors and machines are highly complex, multi-subunit proteins that use chemical energy to perform a multitude of critical, mechanical tasks in cells. The physical mechanisms by which motor proteins (such as myosin and kinesin) transduce chemical energy into mechanical work are still poorly understood. Traditionally, scientists have taken a “top down” approach to addressing this question by determining crystal structures of motor proteins, characterizing mutants and making single molecule measurements of performance.

The goal of our work is to take a “bottom up” approach and design an artificial motor based on non-motor protein components. In this way, we can test our understanding of motor protein operation by including components that have well characterized functional properties. To achieve this, we have set up an international collaborative team comprising our lab plus: Prof. Heiner Linke (Lund University, Sweden); A/Prof. Nancy Forde and Prof. Martin Zuckermann (Simon Fraser University, Canada) and Prof. Dek Woolfson (University of Bristol, UK). Our current design, the Tumbleweed, consists of a three-legged clocked walking protein that operates on a repetitive DNA track. Tumbleweed uses three discrete ligand-dependent DNA-binding domains (repressor proteins) to perform cyclical ligand-gated rectified diffusion along a synthetic DNA molecule.

This project will take the foot-leg assemblies that we are expressing in E. coli and assemble them into the complete heterotrimeric motor. This will use several approaches including intein ligation and Click chemistry (collaboration with Prof. Dek Woolfson). Assays for motor performance will be performed through our motor consortium collaboration (Prof. Heiner Linke and A/Prof. Nancy Forde). We are also investigating new motor designs based on protein modules.

Reference:

Bromley EH, Kuwada NJ, Zuckermann MJ, Donadini R, Samii L, Blab GA, Gemmen GJ, Lopez BJ, Curmi PM, Forde NR, Woolfson DN, and Linke H (2009) The Tumbleweed: towards a synthetic proteinmotor. HFSP journal 3, 204-212. [PubMed link].

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PhD entry requirements

We seek highly motivated candidates with a Class I Honours degree (or equivalent) in modern biological, medical, physical or chemical sciences.  Given the multidisciplinary nature of the projects, there will be a significant training component that will depend on the candidate’s background.  The projects will be funded for three years.  Candidates are expected to apply for an Australian Postgraduate Award (APA)/ University Postgraduate Award (UPA) or International Postgraduate Research Scholarship (IPRS) (or equivalent) and a supplement is available for successful candidates.

Enquiries should be directed to Professor Paul Curmi (p.curmi@unsw.edu.au).