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.
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.
Mechanism Of Neurological Complications In Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$53,609.00
Summary
Malaria kills 1 million young children every year. About the same number are saved by treatment with anti-malarial drugs but have brain damage, leading to problems of understanding, learning or memory. The processes in the brain that lead to these changes are unknown. I will investigate a biochemical pathway that is activated during malaria infection, because I propose that this may cause the brain damage that leads to the long-term cognitive problems in survivors.
A Novel Pathway For The Regulation Of Vascular Tone
Funder
National Health and Medical Research Council
Funding Amount
$596,550.00
Summary
The regulation of blood pressure is complex involving the nervous system, kidneys and local pathways that generate blood vessel relaxing and constricting factors. We recently discovered a novel local pathway that becomes induced during inflammation and generates a relaxing substance from the amino acid tryptophan. The present project will identify the active substance and characterize how it causes blood vessel relaxation and thus contributes to the regulation of blood pressure.
Some bacteria can cause inflammation of the brain (bacterial meningitis). This leads to 170,000 deaths annually in the world. Many patients who survive after antibiotic treatment have lifelong disabilities like deafness, and problems of memory and learning. We aim to show that a certain biochemical pathway in the brain contributes to death and disability, with a view to identifying new drug treatments that can be used alongside antibiotics to improve disease outcomes.
Characterising The Physiological Roles Of The Asparaginyl Hydroxylase FIH-1 In Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$274,743.00
Summary
FIH-1 is an oxygen-sensing protein expressed in every cell. The ability for cells to detect and respond to oxygen deficiency is necessary for survival in heart disease and stroke, and is also a feature of cancer. This research aims to characterise the role FIH-1 plays in normal development and disease using mouse and tumour model systems. This research could ultimately indicate whether FIH-1 is a feasible drug target.