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.
The body’s normal function depends upon maintaining energy balance matching demand and supply. The body senses its energy status by monitoring metabolite concentrations. I have discovered a metabolite that controls multiple enzymes critical for energy homeostasis and appetite in the body that may provide new approaches to tackle obesity related disease. I have found the metabolite-binding pocket in many proteins and it may represent a major new regulatory network.
Investigating The Substrate Specificity Of The Master Kinase LKB1 And The Pharmacological Targeting Of Its Substrate NUAK2 To Treat Cancers
Funder
National Health and Medical Research Council
Funding Amount
$384,768.00
Summary
Kinases are key regulators of cell signaling and emerging drug targets. LKB1 kinase specifically activates a set of substrates to modulate cellular processes, and its substrate NUAK2 is a novel target for cancer. I will elucidate the structural basis of how LKB1 recognizes its substrates and develop inhibitors targeting LKB1-NUAK2 interaction for cancer treatment. My project will provide key insights into kinase-dependent signaling and establish a new framework for therapeutics development.
Host-virus Protein Complexes In The Immune System Response To Influenza
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
This proposal will investigate the inhibition of the human immune response by viruses. Specifically, an enzyme, TRIM25, which ubiquitinates proteins important for signalling the viral immune response has recently been shown to be inhibited by the non-structural influenza protein NS1. The mechanism of this inhibition is unknown and is thus the subject of this project.
Proteins Involved In HIV Infection And Host Defense
Funder
National Health and Medical Research Council
Funding Amount
$323,244.00
Summary
I am a biochemist focused on answering the question: why is it that humans are susceptible to HIV infection, while certain monkeys are resistant? It is known that these monkeys have evolved proteins which can target and destroy the virus, but the equivalent human proteins don’t work against HIV. I intend to compare the monkey and human proteins to understand how the monkeys destroy the virus and why the human protein is defective. These studies will inform the next generation of HIV treatment.
An Integrative Structural Biology Approach To Understanding The SAGA Transcriptional Master Regulator Implicated In Cancer And Development
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Stringent control of gene expression ensures the harmonious life of all human cells. Loss of this control leads to development of a chaotic genome, characteristic of diseased states such as cancer. In this proposal, we aim at capturing and understanding the first key steps of the mechanism that, if dysfunctional, leads to aberrant gene expression. We will use cutting-edge structural bio-imaging to answer questions of fundamental importance to human health and pathologies.
How Do TRIM21 And TRIM5α Execute Dual Antiviral Effector And Signalling Functions?
Funder
National Health and Medical Research Council
Funding Amount
$344,724.00
Summary
We encounter millions of potential pathogens each day that must be detected and disarmed by the immune system. Recently, two antiviral proteins, present inside cells, were shown to both detect viruses, alerting neighbouring cells to the infection, and target the viruses for destruction. These two functions provide important protection against viral infection and this research aims to understand at a molecular level, how these dual antiviral functions are coordinated.