Utility of Cerebrospinal fluid proteomics to define molecular mechanisms in brain disease of childhood.

Summary

Brain diseases of childhood are very common and result in significant disability, and cost to the nation. Common diseases include epilepsy, cerebral palsy, autism and mental health problems. Understanding disease mechanisms is central to future treatments. Taking brain tissue is not possible so the next best tissue to examine is the cerebrospinal fluid, which bathes the brain. Using mass spectrometry approaches to define and quantify proteins, and using large CSF cohorts of patients with common brain diseases, we will improve our understanding of the molecular mechanisms of disease, and also develop prognostic biomarkers

Supervisor(s)

Professor Russell Dale

Research Location

Westmead - Childrens Hospital at Westmead Clinical School

Program Type

Masters/PHD

Synopsis

Brain diseases of childhood, such as epilepsy, cerebral palsy, autism, mental health problems, brain inflammation and neurodegeneration are important, common and disabling problems. Taking brain tissue to examine this process is not possible but taking cerebrospinal fluid via a lumbar puncture is a common procedure that allows clinicians to measure chemicals, to help a diagnosis. However, routine cerebrospinal fluid examination is very basic, yet if we are able to measure the detailed proteome in CSF, we will gain much larger insight in to the disease process. These common diseases have a number of subgroups, with different disease mechanisms. For example, in some conditions there is a brain injury whereas in other conditions, there is brain inflammation, and in others, metabolic failure. Detailed CSF proteomic analysis and quantification will provide major insights in to disease subgroups and provide diagnostic and prognostic information.
This project will develop CSF proteomic technology using mass spectrometry at the Children's Hospital at Westmead and will use extra-ordinary CSF biobanks of over 1000 CSFs from patients with neurological disease- the clinical aspects of this project will be under the supervision of Prof Russell Dale, Professor of Paediatric Neurology. The scientific aspects of CSF mass spectrometry will be under the supervision of Dr Sushil Bandodkar, Head of Biochemistry at Children's Hospital at Westmead.
Defining disease mechanisms has the opportunity to translate in to future treatment trials, by targeting pathways and processes, such as inflammation or metabolic stress.

Additional Information

This project will provide the candidate with expertise in mass spectrometry and other neurochemical techniques and protocols. The candidate will investigate biological sample cohorts of well-defined phenotypes and establish the utility of diagnostic and prognostic biomarkers. The candidate will subsequently translate these novel biomarkers into the routine clinical laboratory.
This project has large clinical translation as the project will use human tissue and therefore directly have relevance to human disease.

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Keywords

Cerebrospinal fluid, Proteomics, brain, child, disease mechanisms

Opportunity ID

The opportunity ID for this research opportunity is: 2481

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