Stem cell to differentiation occurs in a bi-directional fashion. Dedifferentiation which allows specialized cells to become stem cells has been found to be important in both cancer and regeneration. In this proposal, we will investigate the metabolic reprogramming of neuronal dedifferentiation. The findings from this study will better inform us on how to specifically target tumours that arise from dedifferentiation.
Advancing Glycine To The Clinic For Duchenne Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$248,978.00
Summary
We have identified the therapeutic potential of the amino acid glycine for Duchenne muscular dystrophy (DMD), the most common and severe of the muscular dystrophies. To facilitate rapid translation to the clinic, this proposal will; 1) examine the effect of glycine on lifespan and quality of life in mouse models of DMD; 2) determine glycine’s mode of action; and 3) investigate whether these effects represent further benefits to those currently used gold standard treatments.
Ageing And Latelife Health: Calories, Macronutrients Or Branched Chain Amino Acids?
Funder
National Health and Medical Research Council
Funding Amount
$746,459.00
Summary
The prevailing dogma of ageing research has been that a substantive reduction in caloric intake maintained over a lifetime will delay ageing and age-related pathologies (caloric restriction - CR). Yet CR does not differentiate between the effects of reduced intake of calories versus specific macronutrients, nor can it assess the impact of balance of macronutrients. This application seeks to disentangle the role of CR and macronutrients on their effects on healthspan and lifespan in mice.
Targeting Insulin Hypersecretion To Prevent Type 1 And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$834,596.00
Summary
Diabetes develops when islet beta-cells fail to secrete insulin. While major differences exist in the mechanisms by which type 1 and type 2 diabetes develop, there is overlap in beta-cell susceptibility factors. We will investigate whether an islet 'overwork' response to excess nutrient loads underlies beta-cell susceptibility to failure in both types of diabetes. We will also develop novel pharmacological approaches to reduce islet 'overwork' to prevent and treat type 1 and 2 diabetes.
N-Acetyl Cysteine In Schizophrenia Resistant To Clozapine: A Double-Blind Randomised Placebo-Controlled Trial Targeting Negative Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$981,789.00
Summary
Many patients with schizophrenia remain treatment resistant even after “last resort” medications like clozapine. This proposal will conduct a novel multi-site randomised placebo controlled trial of adjunctive N-acetyl cysteine in patients with clozapine resistant schizophrenia. Treatment efficacy will be examined at 8, 26 and 52 weeks.
An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
KYNURENINE PATHWAY METABOLOMIC PROFILING IN THE PROGRESSION OF MULTIPLE SCLEROSIS: DEVELOPMENT OF NOVEL BIOMARKER TO ASSESS DISEASE SEVERITY AND THERAPEUTIC REGIMEN
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
A metabolic process known as the kynurenine pathway (KP) has been found to be dysregulated in multiple sclerosis (MS) patients. We are currently investigating which components of the KP is impaired that put MS patients in jeopardy. Next, we aim to use specific drugs known to manipulate the KP in order to rectify the impairment and stop MS. Outcome of this study may potentially lead to discovery of new biomarkers to assess severity of MS progression and also novel therapeutic regimen.
Neuregulin 1 Type III Overexpression And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$651,966.00
Summary
Neuregulin (NRG1) is a neuronal growth factor and regulates the development of cortical inhibitory interneurons. Human studies suggest that NRG1 type III overexpression and deficient interneuron development underlie schizophrenia. Thus, we have developed a mouse overexpressing Nrg1 type III to discover mechanisms behind NRG1-related cortical pathology and schizophrenia-like behaviours and to clarify whether NRG1 type III interacts with environmental risk factors for the disorder.
The Involvement Of The Kynurenine Pathway In Blood Brain Barrier Disruption And Its Relevance For Neuroinflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$597,797.00
Summary
We aim to study the involvement of molecules deriving from the degradation of the essential amino acid tryptophan on the breakdown of the ñblood-brain barrierî (the cellular wall separating blood and brain) that is observed in several major brain diseases. Using specific drugs blocking the production or the effects of these toxic compounds we expect to be able to preserve the integrity of the blood brain barrier and so to limit brain inflammation and neuronal loss.
Extracellular Acidification And Its Role In Disease
Funder
National Health and Medical Research Council
Funding Amount
$371,529.00
Summary
This proposal focuses on the diseases cystic fibrosis and acute pancreatitis for which there are currently no treatments. In both diseases the affected organs become strongly acidic. Furthermore, these acid changes can be causal in disease progression. However, the source of this acidification is remains unknown. We will identify the routes of acid secretion, the causal role of acidification in disease progression and the effectiveness of treatments aimed at restoring acid-base balance.