About Professor Jill Trewhella

Jill's research seeks a fundamental understanding of the molecular communication that underpins healthy function and who's break down results in diseased states.

Professor Trewhella is a 2004 ARC Federation Fellow who is internationally recognized for her contributions to our understanding of the structural molecular biology of signal transduction.

Jill Trewhella came to the University of Sydney in July 2005 after 25 years in the USA, mostly at Los Alamos National Laboratory, where she led a research effort focused on understanding how cells regulate the molecular activities required for healthy function. In particular she has studied how intracellular “second messengers,” such as Ca2+ and cAMP, relay extracellular signals. Many diseased states are caused by disruptions to these finely controlled signalling mechanisms, and a fundamental understanding of them at the molecular level is an essential underpinning for biomedical research.Jill has taken a unique approach to studying these systems by using biophysical tools, such as small-angle X-ray solution scattering and neutron contrast variation in combination with crystallography, NMR and computational methods, to probe how proteins communicate signals from one to another via conformational dynamics and global shape changes.  While crystallography and NMR can provide exquisitely detailed structures of individual bio-molecules, and in special cases even of large assemblies can be crystallized for high resolution analysis, solution scattering techniques can provide information on large complexes or assemblies of molecules even when there is inherent flexibility – as is often a requirement for proper function.Since returning to Sydney in 2005, Jill has established a research team that is studying signalling mechanisms in a variety of systems including the receptor/ligand partners of nerve synapses in order to understand the molecular mechanisms of neuronal disorders such as autism, bacterial histidine kinases as a foundation for the potential development of novel therapeutics for fighting infectious diseases, and protein complexes involved in muscle contraction and are important for healthy heart function.  Jill is also working with leading crystallographic and NMR labs on methodology development for combining hybrid data from different techniques to develop a more complete picture of the structure and dynamics of biomolecules and the complexes they form in order to carry out their highly specialized functions.

Selected publications

  • Comoletti, D., Grishaev, A., Whitten, A.H., Tsigelny, I., Taylor, P. and Trewhella, J. Small-Angle Solution Scattering of the Neuroligin/β-Neurexin Complex Reveals its Synaptic Arrangement,” Structure 15, 693-705, 2007.  PubMedId: 17562316
  • Whitten, A. E., Jacques, D. A., Hamouda, B., Hanley, T., King, G. F., Guss, M. J., Trewhella, J. and Langley, D. B., The Structure of the Sda-KinA Complex Suggests an Allosteric Mechanism of Histidine Kinase Inhibition,” J. Mol. Biol. 368, 407-420, 2007. PubMedId: 17350039
  • Vigil, D., Blumenthal, D. K., Taylor, S. S., and Trewhella, J. “Solution Scattering Reveals Large Differences in the Global Structures of Type II Protein Kinase A Isoforms,” J. Mol. Biol. 357, 880-889, 2006. PubMedId: 16460759
  • Grishaev, A., Wu, J., Trewhella, J., and Bax, A. “Refinement of Multi-Domain Structures by Combination of Solution Small-Angle X-ray Scattering and NMR Data,” J. Am. Chem. Soc. 127, 16621- 16628, 2005. PubMedId: 16305251
  •  Vigil, D., Blumenthal, D. K., Brown, S., Taylor, S. S., and Trewhella, J. “Differential Effect of Substrate on Type I and Type II PKA Holoenzyme Dissociation” Biochemistry 43, 5629-5636, 2004. PubMedId: 15134437
  • Heller, W. T., Finley, N., Dong, W.-J., Timmins, P., Cheung, H. C., Rosevear, P. R., and Trewhella, J. “Small-Angle Neutron Scattering with Contrast Variation Reveals Spatial Relationships Between the Three Subunits in the Ternary Cardiac Troponin Complex and the Effects of Troponin I Phosphorylation,”  Biochemistry 42, 7790-7800, 2003. PubMedId: 12820888
  • Wall, M. E., Francis, S. H., Corbin, J. D., Grimes, K., Richie-Jannetta, R., Kotera, J., Macdonald, B. A., Gibson, R. R., and Trewhella, J., “Mechanisms Associated with cGMP Binding and Activation of cGMP-Dependent Protein Kinase,” Proc. Natl Acad. Sci. USA 100, 2380-2385, 2003.  PubMedId: 12591946
  • Krueger, J. K., Gallagher, S. C., Zhi, G., Geguchadze, R., Persechini, A., Stull, J. T., and Trewhella, J. “Activation of Myosin Light Chain Kinase Requires Translocation of Bound Calmodulin,” J. Biol. Chem. 276, 4535-4538, 2001. PubMedId: 11124250
  • Sunnerhagen, M., Olah, G. A., Stenflo, J., Forsén, S., Drakenberg T., and Trewhella, J. “The relative orientation of Gla and EGF domains in coagulation factor X is altered by Ca2+ binding to the first EGF domain. A combined NMR small angle X-ray scattering study,” Biochemistry 35, 11547-11559, 1996. PubMedId: 8794734
  • Heidorn, D.B., and Trewhella, J. “Comparison of the Crystal and Solution Structures of Calmodulin and Troponin C,” Biochemistry 27, 909-915, 1988.  PubMedId: 3365370