Discovering The Function And Structure Of RIO Kinases – Toward New Nematocides
Funder
National Health and Medical Research Council
Funding Amount
$545,477.00
Summary
This project is focused on: high quality fundamental molecular science, contributing to national objectives, including the development of novel and innovative scientific concepts and international collaborations; consolidating links between basic and applied research; enhancing the skills-base in molecular biology and global visibility of Australian science.
Mechanistic Characterisation Of The Epigenetic Modifier Smchd1
Funder
National Health and Medical Research Council
Funding Amount
$1,197,133.00
Summary
FSHD is a progressive muscular dystrophy that currently has no treatment or cure. SMCHD1 is known to play an important role in FSHD, where its usual function in switching genes off is imperfect, contributing to disease. In this project we will determine how SMCHD1 switches genes off and what SMCHD1 looks like at the molecular level, so that we can elucidate how to boost SMCHD1 function for FSHD therapy.
My research is aimed at understanding how the structure and dynamics of proteins dictates their function. I use X-ray crystallography to determine the shapes of proteins. Proteins are not static, however - they move in complicated ways, and often their motion is critical to their function (molecular motors, for example). It is very difficult to 'watch' this movement in the lab, so I use computer simulation to try to understand how proteins move.
Proteases, Their Inhibitors And Receptors In Degenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,843,388.00
Summary
Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin super ....Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin superfamily of protease inhibitors and their protease partners. He is currently the scientific director of the Victorian Bioinformatics Consortium and an NHMRC Senior Research Fellow. Dr Bird is an NHMRC Senior Research Fellow who discovered the intracellular branch of the serpin superfamily and formulated the hypothesis that describes their function. A-Prof Mackie is a world expert in the field of musculoskeletal biology and pathology. Dr Bottomley is a Senior Logan Fellow and RD Wright Fellow whose research focuses upon how proteins misfold and lead to disease. Dr Pike is an enzymologist whose research area encompasses a wide range of bacterial and mammalian proteases involved in the pathology of human disease. Each individual in this team brings different skills which makes this a very important and powerful collaboration. The research is extensive and involves protein folding, enzyme kinetics, molecular modelling, structural biology, bioinformatics, cell biology and pathology, enzyme kinetics and drug design. Collectively the CI’s have a total of 154 papers since 1998, of which a third include two or more of the CI’s as co-authors. Currently the team holds over >$5 million in grant funding. The team is augmented by four P.I.s: Dr Buckle is a talented structural biologist; Dr Scott is a molecular cell biologist who holds an NHMRC CJ Martin Fellow; Dr Garcia de la Banda is a computer scientist based at Monash and Dr Grigoryev is a world expert in chromatin condensation based at Penn State University (USA).Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101323
Funder
Australian Research Council
Funding Amount
$427,098.00
Summary
Structure guided mapping of protein interactions and their perturbation. Protein interactions are central to most biological processes, and significant effort has been devoted to trying to unravel these complicated networks. This project aims to develop new approaches to better understand these interactions, and the consequences of their perturbation. The main expected contributions will be: (i) methods to identify likely protein interaction sites using population conservation; (ii) computationa ....Structure guided mapping of protein interactions and their perturbation. Protein interactions are central to most biological processes, and significant effort has been devoted to trying to unravel these complicated networks. This project aims to develop new approaches to better understand these interactions, and the consequences of their perturbation. The main expected contributions will be: (i) methods to identify likely protein interaction sites using population conservation; (ii) computational approaches to assess the effects of any type of mutation on the interaction; and (iii) an understanding of how disruption of a specific interaction can affect the complicated biological network within a cell. Read moreRead less
Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins ....Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins of high biochemical or biomedical importance, and the approach will be applied to established drug targets.Read moreRead less
Three-dimensional structure determination of biomolecular assemblies from sparse data of different length scales. New computer algorithms will be combined with sparse experimental structure restraints, obtained with novel protein chemistry technologies, to generate accurate three-dimensional (3D) models of proteins and protein assemblies in solution and in the solid state. The new strategies will greatly increase the number of protein targets amenable to rational drug design.
The Development Of Novel Antibody Constructs And Peptides To Prevent Pathogenic Modulation Of The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$335,825.00
Summary
The current lack of effective vaccines, as well as the emergence of drug resistance, underpins the need for the development of novel therapeutics to treat bacterial infections and malaria. In this project, I will be using computer-based molecular modelling techniques to design novel antimicrobial treatments.
Investigating Post-transcriptional Gene Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In this program, I will enhance our understanding of cancer gene regulation and provide novel avenues for the treatment of aggressive tumours. Using own data and that from collaborators, I will determine patterns of gene regulation in blood cancers and identify markers that predict disease outcome. I aim to understand how gene regulation can transform healthy cells into tumour cells and whether personalised treatment can kill tumour cells more effectively and prevent relapse and metastasis.
Integrated System Wide Characterization Of Microbiota And Host Factors Influencing Intestinal Colonization Resistance To The Healthcare Pathogen Clostridium Difficile
Funder
National Health and Medical Research Council
Funding Amount
$359,999.00
Summary
Naturally occurring bacteria play an important role in determining patient disease susceptibility, disease progression and ultimately, disease outcome. Over 1000 species of bacteria, contributing 10 times as many cells as found within a single individual. This project seeks to understand these communities, how they confer resistance to infection and how they can be manipulated, both naturally and through controlled introduction of bacteria to prevent disease or improve disease outcome.