Nuclear architecture is critical to the preservation of genome integrity. The aim of this research proposal is to delineate the role of chromatin organisation in transcription factor target search and damage site recruitment of DNA repair factor machinery. To achieve this I have developed fluorescence microscopy methods to monitor changes in chromatin structure with submicron resolution. Only with this technology can I determine how chromatin dynamics maintain genome integrity or induce disease.
Structural And Drug Discovery Studies Of Medically Important Protein Complexes
Funder
National Health and Medical Research Council
Funding Amount
$438,577.00
Summary
My research is focused on structural studies of medically important biological systems, where specific protein complex formation contributes to human illnesses. I use X-ray crystallography to visualize the whole complex at atomic resolution as well as to determine whether binding partners have undergone changes in shape upon complex formation. This structural information then helps me in drug design with goals to either disrupt or modulate the complex.
Understanding Allosteric Modulation And Biased Signalling At Family B GPCRs
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
Family B GPCRs are therapeutic targets for drugs treating osteoporosis, hypercalcaemia, Paget’s disease, type II diabetes and are being actively pursued for other diseases that represent major global health burdens. Despite huge financial input, there are no orally available drugs that act on these receptors. This speaks to a lack of mechanistic understanding of how they work. My research focuses on addressing this question and how to exploit these receptors to design and identify better drugs.
Assembly Of Mitochondrial Respiratory Chain Complexes And Their Defects Associated With Disease.
Funder
National Health and Medical Research Council
Funding Amount
$413,431.00
Summary
Mitochondrial “respiratory chain complexes are multi-subunit assemblies that function to produce most of our cellular energy. Defects in the assembly of these complexes can result in mitochondrial disease, including infant death. The assembly of the respiratory complexes is a complicated procedure and the mechanisms involved in disease remain elusive. This work will aid in our understanding of how these protein complexes are built and how defects in their assembly can cause disease.