Stephen Fairweather

My research focuses on the biochemistry and physiology of membrane transporter proteins. Membrane transporters exist in all biological membranes and mediate the flux of nutrients, ions, and xenobiotics both in and out of living cells. We use molecular biology, biochemical and analytical chemistry methods for the investigation of structure-activity relationships in these proteins. Current research interests include elucidating the identity, function and importance of amino acid transporters in the major human pathogens from the phylum Apicomplexa: Toxoplasma gondii and Plasmodium spp. I am currently employed as a post-doctoral scientist in the Laboratories of Assoc. Prof. Giel van Dooren and Prof. Stefan Bröer in the Research School of Biology and am enjoying working with the molecular parasitologists, combining the study of isolated transporters proteins with the genetics and cell biology methods that my brilliant colleagues use to study these organisms. I am immensely interested in showing how the chemistry of membrane transporters are vital for understanding their more obviously manifest biological and physiological roles in the whole organisms. I enjoy very much applying new techniques into the novel setting of membrane physiology. Recently this includes widening our research expertise to incorporate high resolution metabolomic techniques such as GC-QQQ and LC-MS/MS, and the expression of apicomplexan membrane proteins in yeast and X.laevis oocytes for high-resolution functional and structural analysis of these proteins.

Research interests

Membrane Physiology and Transporters

Protein-Protein Interactions

Electrophysiology

Amino Acid Metabolism

Membrane Transporter Phamacology

Protein Molecular Dynamic Simulations

 

Awards and Grants

Title: Australasian Leadership Computing Grants COVID-19 Special Call Grant 2020

Title of Project: Using large-scale molecular dynamics for rational drug design

Description: Stephen Fairweather is the recipient along with Assoc. Prof. Megan O'Mara and Dr Katie Wilson, of the NCI Australasian Leadership Computing Grants COVID-19 Special Call Grant 2020.

This research uses simulations of the around 800,000 atoms that make up a key receptor of the human body to understand exactly how the coronavirus uses it to invade human cells. It is only with high-resolution modelling that accurately replicates the true behaviours of these receptors that we can figure out where vulnerabilities in the virus’ binding process are. Targeting the interaction between the human receptors and the coronavirus binding protein might well be a useful direction for drug design. This project will produce world-first vital information about regions of the receptors that could be potential vaccine or drug targets. Using 48 processors running for 19 days for each of 64 molecular simulations, this research will spend around 13 million hours of computing time in the coming months. This amount of high-performance computing is only available on NCI’s new Gadi supercomputer.

Valued at: 13 Million NCI Service Units ($600,000 AUD)

Website Link: Special Announcement: ALCG COVID-19 Special Call Recipients | NCI

 

Title: The Australian Physiological Society PhD research training award

Description: Stephen Fairweather is the recipient of the Australian Physiological Societies PhD Research Training Award. The Award is Competitively selected and pays expenses for a PhD candidate to visit to laboratories in the Asia-Pacific. Stephen Will use the funds to visit and learn new electrophysiological techniques from laboratories at The University of NSW's School of Biomedical Sciences in the William Wurth Building.

Valued at: $500 AUD

Website Link: aups.org.au/Prizes/

 

  • S. L. Neville, J. Sjöhamn, J. A. Watts, H. MacDermott-Opeskin, S. J. Fairweather, K. Ganio, A. C. Hulyer, A. J. Hayes, A. P. McGrath, T. .R. Malcolm, M. R. Davies, N. Nomura, I. So, M. L. O'Mara, C. A. McDevitt and M. J. Maher 2021, 'The structure of the ABC transporter PsaBC shows that bacterial manganese import is achieved by unique architectural features that are conserved across the kingdoms of life', Acta Crystallographica Section A: Foundations and Advances 77(a2):C100-C100.
  • Wilson, K, Fairweather, S, Macdermott-Opeskin, H et al. 2021, 'The role of plasmalogens, Forssman lipids, and sphingolipid hydroxylation in modulating the biophysical properties of the epithelial plasma membrane', Journal of Chemical Physics, vol. 154, no. 9.
  • Fairweather, S, Okada, S, Gauthier-Coles, G et al. 2021, 'A GC-MS/Single-Cell Method to Evaluate Membrane Transporter Substrate Specificity and Signaling', Frontiers in Molecular Biosciences, vol. 8, pp. 1-21.
  • Fairweather, S, Gupta, V, Chitsaz, M et al. 2021, 'Coordination of Substrate Binding and Protonation in the N. gonorrhoeae MtrD Efflux Pump Controls the Functionally Rotating Transport Mechanism', ACS Infectious Diseases, vol. 7, no. 6, pp. 1833-1847.
  • Neville, S, Sjohamn, J, Watts, J et al. 2021, 'The structural basis of bacterial manganese import', Science Advances, vol. 7, no. 32.
  • Fairweather, S, Rajendran, E, Blume, M et al. 2021, 'Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii, PLoS Pathogens, 17, https://doi.org/10.1371/journal.ppat.1009835
  • Fairweather, S, Shah, N & Broer, S 2020, 'Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology', in JD Ash, RE Anderson, M LaVail, C Bowes Rickman, JG Hollyfield, C Grimm (ed.), Advances in Experimental Medicine and Biology, Springer Singapore, Singapore, pp. 1 - 115.
  • Javed, K & Fairweather, S 2019, 'Amino acid transporters in the regulation of insulin secretion and signalling', Biochemical Society Transactions, vol. 47, no. 2, pp. 571-590.
  • Broer, S & Fairweather, S 2019, 'Amino Acid Transport Across the Mammalian Intestine', Comprehensive Physiology, vol. 9, no. 1, pp. 343-373pp.
  • Parker, K *, Fairweather, S *, Rajendran, E et al. 2019, 'The tyrosine transporter of Toxoplasma gondii is a member of the newly defined apicomplexan amino acid transporter (ApiAT) family', PLoS Pathogens, 15, e1007577.
    * Co-first authors
  • Broer, A, Fairweather, S & Broer, S 2018, 'Disruption of Amino Acid Homeostasis by Novel ASCT2 Inhibitors Involves Multiple Targets', Frontiers in Pharmacology, vol. 9, no. 785, pp. 1-11pp.
  • Cheng, Q, Shah, N, Broer, A et al. 2017, 'Identification of novel inhibitors of the amino acid transporter B0AT1 (SLC6A19), a potential target to induce protein restriction and to treat type 2 diabetes', British Journal of Pharmacology, vol. 174, no. 6, pp. 468-482pp.
  • Rajendran, E, Hapuarachchi, S, Miller, C et al 2017, 'Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites', Nature Communications, 8:14455. doi: 10.1038/ncomms14455.
  • Morton, S, Chaston, D, Howitt, L et al 2015, 'Loss of functional endothelial connexin40 results in exercise-induced hypertension in mice', Hypertension, vol. 65, no. 3, pp. 662-U362.
  • Fairweather, S, Broer, A, Subramanian, N, Tumer, E, Cheng, Q, Schmoll, D, O'Mara, ML, Bröer, S. 2015, 'Molecular basis for the interaction of the mammalian amino acid transporters B0AT1 and B0AT3 with their ancillary protein collectrin', Journal of Biological Chemistry, vol. 290, no. 40, pp. 24308-24325.
  • Fairweather, S, Broer, A, O'Mara, M et al 2012, 'Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1', Biochemical Journal, vol. 446, no. 1, pp. 135-148.