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  How to stop an epileptic seizure - looking for the right molecules to target


   Synapse Proteomics Group

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  Dr Mark Graham  Applications accepted all year round  Funded PhD Project (Students Worldwide)

About the Project

Summary: Hundreds of proteins are implicated in epilepsy. This project involves interrogating models of epilepsy to determine which are the key pathways and molecular mechanisms which could be targeted to prevent or stop an epileptic seizure. Proteomics and phosphoproteomics is being used to deep screen signalling pathways in epilepsy model systems including animals and iPSC-derived organoids. Key pathways will be functionally validated and targeted using drugs and genetic tools. In parallel, biomarkers that indicate epilepsy stages and the best treatments for patients are being investigated.

Synopsis: The Synapse Proteomics group uses cutting edge proteomics and bioinformatics (1) analysis to understand both normal and perturbed brain function. Many aspects of how brains adapt to stimuli at the cellular and molecular level are unknown. Phospho-signalling is the earliest marker of proteins and pathways that are involved in neuronal activity and precede protein expression changes. We discover both signalling and changes in protein expression using phosphoproteomics and proteomics in deep screens that result in data sets of tens of thousands of phosphorylation sites. This data is simplified using bioinformatics tools. The screens are followed functional assays to verify new mechanisms that can potentially be exploited to develop therapeutics for diseases. These functional analyses may use genetic tools such as CRIPSR-Cas9, viral vectors, knock out animal models or iPSC-derived organoids in combination with electrophysiology and microscopy. In parallel, blood from animal models and patients can be screened for biomarkers using proteomics.

Research environment: This project will be conducted at Children’s Medical Research Institute (CMRI), an award-winning state-of-the-art medical research facility, with over 100 full-time scientists dedicated to researching the genes and proteins important for health and human development. CMRI is supported in part by its key fundraiser Jeans for Genes®. Our scientists are internationally recognised research leaders and foster excellence in postgraduate training. CMRI graduates are highly sought after nationally and internationally.

CMRI is located in western Sydney on the Westmead medical precinct, a major hub for research and medicine in NSW, and is affiliated with the University of Sydney. Easy to access by public transport.

 Eligibility requirements:  Applicants must hold:

     a relevant Bachelor’s degree with first or second class Honours, OR

○     a research Master’s degree, OR

○     at least 6 months of supervised research training

○     Applicants must be available to start a full-time PhD at CMRI within 6 months.

 ○    International students are eligible to apply, but the CMRI scholarship does not cover university tuition fees. International students will need to apply for additional scholarships to cover these fees.

 How to apply:  

1)  Contact the supervisor for this project (Dr Mark Graham), enclosing your CV and academic transcripts, and explaining why your research background is a good fit for the research in our laboratory.

 2)  If invited, submit an application using the application form available on the CMRI website (https://www.cmrijeansforgenes.org.au/research/opportunities-for-research-students/cmri-phd-research-award). 

Biological Sciences (4) Chemistry (6) Medicine (26)

Funding Notes

Applicants will be assessed in a competitive process involving an interview. Successful applicants will be awarded a CMRI Research Award (https://www.cmrijeansforgenes.org.au/research/opportunities-for-research-students/cmri-phd-research-award), consisting of a generous top-up over the value of a university scholarship. Successful applicants will also be expected to apply for external scholarships.

References

1. Engholm-Keller, K., et al., The temporal profile of activity-dependent presynaptic phospho-signalling reveals long-lasting patterns of poststimulus regulation. PLoS Biol, 2019. 17(3): p. e3000170.
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