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ZFIN ID: ZDB-LAB-110607-1
Tennore Ramesh Lab
PI/Director: Tennore, Ramesh
Contact Person: Tennore, Ramesh
Address: Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN) University of Sheffield 385a Glossop Road Sheffield S10 2HQ United Kingdom
Country: United Kingdom
Phone: +(44) (0)1142222246
Fax: +(44) (0)2222290
Line Designation: sh

Show all 2 genomic features

Despite the identification several genes causing amyotrophic lateral sclerosis (ALS) the exact mechanism of motor neuron toxicity is unclear. Relatively little is known about when and how the disease, which starts focally, spreads throughout the motor network. We also do not know the precise mechanism by which the mutant proteins causes toxicity. My lab focuses on these two dominant questions to investigate the pathogenesis of ALS

Role of protein misfolding: The role of protein misfolding and cellular inclusions is a common theme in many neurodegenerative diseases including ALS. The focus of my research is to understand how protein misfolding contributes to toxicity and identify early cellular events that result from expression of mutant proteins. My lab has developed a transgenic fish overexpressing mutant sod1. These fish show all the characteristic features of ALS seen in humans and mice. We have also developed a reporter system to monitor cellular stress due to expression of mutant protein and utilise it to identify early cellular changes before onset of overt clinical symptoms.

Neuronal circuitry in ALS: Although ALS is considered a motor neuron disease, it also affects other neuronal and non-neuronal cell types. Zebrafish embryos are transparent and it easy to monitor individual neurons and their connections to other neuronal groups in a living fish. We have developed a reporter system to track neuronal stress in our mutant sod1 transgenic fish all the way from the CNS to the target muscle they innervate. By identifying stressed neurons we can study the electrophysiology of these stressed neurons and study how changes in stressed neurons affect the neuronal circuitry and eventually the spinal motor neurons and the muscle they innervate to produce a motor output. My lab uses the advantages of zebrafish to study disease process at a single cell resolution level to trace the origins of disease process in a complex living and swimming organism.

Hewamadduma, Channa A. Graduate Student McGown, Alexander Graduate Student

Shaw, M.P., Higginbottom, A., McGown, A., Castelli, L.M., James, E., Hautbergue, G.M., Shaw, P.J., Ramesh, T.M. (2018) Stable transgenic C9orf72 zebrafish model key aspects of the ALS/FTD phenotype and reveal novel pathological features. Acta neuropathologica communications. 6:125
Chhabria, K., Plant, K., Bandmann, O., Wilkinson, R.N., Martin, C., Kugler, E., Armitage, P.A., Santoscoy, P.L., Cunliffe, V.T., Huisken, J., McGown, A., Ramesh, T., Chico, T.J., Howarth, C. (2018) The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 40(2):298-313
Burrows, D.J., McGown, A., Jain, S.A., De Felice, M., Ramesh, T.M., Sharrack, B., Majid, A. (2018) Animal models of multiple sclerosis: From rodents to zebrafish. Multiple sclerosis (Houndmills, Basingstoke, England). 25(3):306-324
McGown, A., Shaw, D.P., Ramesh, T. (2016) ZNStress: a high-throughput drug screening protocol for identification of compounds modulating neuronal stress in the transgenic mutant sod1G93R zebrafish model of amyotrophic lateral sclerosis. Molecular neurodegeneration. 11:56
Seytanoglu, A., Alsomali, N.I., Valori, C.F., McGown, A., Kim, H.R., Ning, K., Ramesh, T., Sharrack, B., Wood, J.D., Azzouz, M. (2016) Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo. Neuroscience. 322:287-97
Hewamadduma, C.A., Grierson, A.J., Ma, T.P., Pan, L., Moens, C.B., Ingham, P.W., Ramesh, T., and Shaw, P.J. (2013) Tardbpl splicing rescues motor neuron and axonal development in a mutant tardbp zebrafish. Human molecular genetics. 22(12):2376-86
McGown, A., McDearmid, J.R., Panagiotaki, N., Tong, H., Al Mashhadi, S., Redhead, N., Lyon, A.N., Beattie, C.E., Shaw, P.J., and Ramesh, T.M. (2013) Early interneuron dysfunction in ALS: Insights from a mutant sod1 zebrafish model. Annals of neurology. 73(2):246-258