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Satish Nemani, PhD and Valerie L Sim, MD, FRCPC

Grant Title: Contribution of oligomeric prion populations to phenotypic heterogeneity in variably protease-sensitive prionopathy (VPSPr) versus silent prions

Location: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada

Grant Year: 2023

Prion disease starts when the normal prion protein folds into the wrong shape then causes other prion proteins to fold into the wrong shape and clump together, creating a domino-like effect of misfolded prion proteins that spread through the brain. Interestingly, sometimes these clumps of misfolded prion protein are found in normal brains where there is no sign of disease. Why can’t these “silent prions” transmit disease? We think the clue lies in their unique misfolded size and shape, which may affect their stability, toxicity, or ability to induce other toxic proteins to misfold. We propose to compare the size, shape and stability of these silent prions to more infectious prions in order to understand why one lies dormant while the other causes devastating disease.

About the Researchers:

Valerie L Sim, MD, FRCPC
Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada

Dr. Valerie Sim is a prion scientist at the Centre for Prions and Protein Folding Diseases at the University of Alberta, and a clinical neurologist at the University of Alberta Hospital, in Edmonton, AB, Canada. She is medical director of the Canadian CJD Association and co-founder of the Edmonton Cognitive Neurology clinic.

After her obtaining her BSc(Hon) and MD at the University of Calgary, followed by neurology residency at University of Ottawa, Dr. Sim completed a post-doctoral fellowship in prion disease research at Rocky Mountain Laboratories, NIH, Montana, under the supervision of Dr. Byron Caughey. She joined the University of Alberta Division of Neurology in 2009 and was promoted to associate professor with tenure in July, 2016.

In her research lab, Dr. Sim is interested in understanding how a prion’s size and shape can influence patterns of disease and risks of transmission. She isolates prion particles from infected brain samples using asymmetric flow field-flow fractionation, and examines pathogenesis in a “prion-disease-in-a-dish” brain slice culture model. From light scattering analysis and protein biochemistry to animal treatment experiments, her research publications have received international media attention.

She is also passionate about promoting science communication and has published a TEDx talk on prion disease. She regularly presents the science of prion disease to diverse communities across Alberta, Canada, and internationally.

Satish Nemani, PhD
Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada

Dr. Satish Nemani is a Postdoctoral Fellow in the laboratory of Dr. Valerie Sim at the Centre for Prions and Protein Folding Diseases, University of Alberta.

After obtaining his PhD at the Leibniz University of Hannover, Germany, Satish Nemani pursued his first post-doctoral fellowship at Case Western Reserve University, Cleveland, under the supervision of Dr. Pierluigi Gambetti. To expand his understanding of prion diseases he joined Dr. Sim’s lab in 2019, where he has been working on prion strain characterization by developing methods to identify subtle differences within prion strains. He is primarily interested in developing an assay for the identification of distinct prion strains during antemortem diagnosis, which could lead to novel therapeutics strategies in the future. Currently, he is working on isolating the heterogeneous oligomeric populations from atypical sporadic Creutzfeldt-Jakob disease (sCJD) subjects as well as typical sCJD subjects to identify oligomers that may be associated with phenotypic variability within the prion strains in terms of disease pathology and presentation.

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