Research Projects

This research will explore mechanisms associated with the development of progressive multiple sclerosis (MS). This project will use specialised techniques for analysing the ways that genes are switched on and off, such as DNA methylation and gene expression patterns, within grey matter brain tissue from a region called the thalamus. The researchers will compare between tissue from people affected by MS, compared to ‘control’ tissue from people who did not have any neurological disease.

This research will examine examine the full profile of miRNAs in MS lesions and neighbouring normal appearing tissue. Using specialised technoilogy, highly accurate data will be obtained from very small amounts of tissue. The specific miRNAs are tagged with fluorescent barcodes and then accurately counted via microscopic images. The team will determinewhen neurodegenerative processes occur in the brains of people with secondary progressive MS.

A small region in the brain, the locus ceruleus, has been shown to be damaged in MS, and is also the region in the brain that takes up circulating toxins most avidly. This project will test the locus ceruleus in people who had MS to look for the presence of heavy metal toxins, as a preliminary study to determine if heavy metal toxins may play a role in MS onset.

The exact target of the self-immune response in MS is yet to be identified. This project will use advanced proteomics to discover and characterise these protein targets and other important proteins in MS. Proteomics allows scientists to examine all the proteins in a biological situation at once – potentially thousands of proteins in the brain. The project is examining brain tissue taken from differently affected areas of the brain and spinal cord to determine which proteins are involved at the very earliest stages of MS lesion development or lesion expansion. This will eventually lead to more targeted therapies for MS.

Ly L, Barnett MH, Zheng YZ, Gulati T, Prineas JW, Crossett B. (2011) Comprehensive Tissue Processing Strategy for Quantitative Proteomics of Formalin-fixed Multiple Sclerosis Lesions. J Proteome Res., 10 (10): 4855-68. doi: 10.1021/pr200672n, PMID: 218708544

Optic neuritis is a frequent initial manifestation of MS and is often used as a model for studying the mechanisms of axonal loss and myelination in MS. In contrast to most brain regions the optic nerve has a simple, regular structure and no nerve cell bodies, making it more straightforward to study. In this project, MS-affected optic nerve specimens will be analysed by staining the cells involved with repair of damaged nerve sheaths (remyelination) to find out why this process fails in later phase MS. By understanding more about ‘remyelination failure’ it is hoped that researchers can find a way to prevent it happening and therefore improve patient health outcomes.

The reasons for the failure of the nervous system to recover after injury in MS are unclear. Understanding the mechanisms that control myelin regeneration of the neurons are crucial in identifying new treatments and potentially a cure for MS. This project will study a particular type of protein called leukocyte immunoglobulin-like receptor-A3 (LILRA3) that are known to promote nerve repair. Associate Professor Tedla will study roles of these proteins in MS and explore the potential use of these proteins as new treatment strategy aimed at reducing or preventing debilitating neuronal damage in MS.