THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
The Effect Of Stress And Hypercortisolaemia On Limbic Epileptogenesis & Affective Disorder.
Funder
National Health and Medical Research Council
Funding Amount
$380,714.00
Summary
This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is ....This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is a bi-directional relationship, with the psychiatric conditions and stress also acting to aggravate the seizures and even predispose to the development of the epilepsy itself. Apart from gaining insights into causes of TLE, anxiety and depression, this framework has potential public health relevance suggesting approaches to the eventual primary and secondary prevention of both MTLE and its associated psychiatric co-morbidities, a neglected area at present. The use of an animal model allows investigation of aetiological processes that extend over the lifetime, which is exceptionally difficult to achieve in humans. Retrospective studies, such as case-control studies, although an indispensable research methods, are subject to bias and imprecision when it comes to measuring remote past exposures to stress, abuse, and deprivation. If the results of these experiments are consistent with our hypotheses, a very strong case would exist for exploring this relationship in human studies. The data would also provide a strong rationale for more aggressive detection and treatment of these psychiatric co-morbidities in TLE patients, in order to potentially modify the progression of the disorder as well as improve the quality of life of sufferers. The results of intervention studies in animal models may suggest specific mode of treatment to achieve this.Read moreRead less
Why Does Early Life Stress Aggravate Limbic Epileptogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$540,116.00
Summary
High rates of anxiety and depression occur in individuals with temporal lobe epilepsy (TLE), the most common form of focal epilepsy in adults. Rats that have experienced early life stress show increased anxiety, decreased seizure thresholds and accelerated epilepsy as adults. We have important leads to mechanisms. The proposed study will better understand the mechanisms connecting early life stress and psychiatric disease to adult TLE, and to test interventions that may counteract these effects.
Development and application of new peptide ligation methods for the synthesis and structure-function studies of glycoproteins. Novel synthetic technologies will be developed in this project to facilitate the preparation of glycoproteins, which are of widespread biological and therapeutic interest. These methods will enable the preparation of pure glycoproteins for detailed biochemical and functional studies eventually leading to therapeutic and diagnostic applications.
Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC is ....Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC isoforms with desirable properties. Ultimately, the project aims to identify isoforms that improve plant fitness under stress conditions. Optimising PEPC activity will provide next generation solutions to improve water balance and carbon assimilation to keep C4 crops productive under future climates.Read moreRead less
Functional studies of tyrosine sulfation using synthetic sulfoproteins. This project aims to address a lack of knowledge about how post-translational sulfation of tyrosine residues influences protein function. The project will develop a synthetic platform for the rapid and efficient generation of libraries of site-selectively sulfated proteins. The new methods will be used to study bioactive sulfated proteins secreted by ticks that dampen the inflammatory response and prevent blood from clotting ....Functional studies of tyrosine sulfation using synthetic sulfoproteins. This project aims to address a lack of knowledge about how post-translational sulfation of tyrosine residues influences protein function. The project will develop a synthetic platform for the rapid and efficient generation of libraries of site-selectively sulfated proteins. The new methods will be used to study bioactive sulfated proteins secreted by ticks that dampen the inflammatory response and prevent blood from clotting. Underpinned by the ability to access synthetic sulfoproteins, expected outcomes include a detailed understanding of how tyrosine sulfation can modulate function and stability of antibodies and proteins with anticoagulant and anti-inflammatory activities. Significant benefits of the project will include breakthrough technologies for the preparation of homogeneously modified proteins, which will strengthen Australia’s growing biotechnology sector.Read moreRead less