MK

Manjeet Kumar

University of Michigan, University of Alberta, Australian National University

ORCID iD 0000-0001-5355-9041
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About

Misfolded, aggregated, non-functional proteins and peptides within the cell are implicated with more than 55 pathological conditions including various neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Prions and haemodialysis-related amyloidosis, which together affect more than 24 million people worldwide.

My PhD thesis has attempted to address some of the issues discussed above, to assist in advancing the understanding of the complexities of protein misfolding, aggregation and their mitigation.
The results documented in my dissertation have assisted in advancing our knowledge and understanding of the molecular, biophysical and biochemical mechanisms of amyloid fibril formation. In addition, my PhD thesis determined the broader applicability of TPE-TPP compared to the standard amyloid dye (i.e. ThT) as a fluorescent probe to monitor amyloid fibril formation, detect early-stage aggregates, variations in fibril morphologies, and can be deemed useful in screening amyloid inhibitors. Part of the aim to identify and characterise various protein aggregate species was to develop a method for regulating potentially toxic entities. I showed that intra- (αB-crystallin) and extra-cellular (clusterin) molecular chaperones were capable of acting on different stages of D76N β2m aggregation, thereby reducing the effects of undesirable, misfolded toxic protein forms. Furthermore, I demonstrated that there could be other potentially hazardous forms of unwanted protein aggregates (i.e. βS self-assembled structures) that are not necessarily amyloid fibrils. Greater comprehension of protein aggregation will not only shed light on protein conformational disorders and aid in the development of therapeutics against their toxic effects, but may also offer insights into opportunities for exploiting stable, non-toxic protein conformations to our advantage.

My postdoctoral work in Canada aimed to isolate different prion strains using immunoprecipitation from field-flow fractionated healthy mouse brain homogenate, and a scrapie-infected cell line using streptavidin magnetic beads. Subsequent quality control of these samples are performed by SDS-PAGE and Western Blotting, with further strain amplication using PMCA. Secondly, we developed a method for the soluble expression and purification of recombinant prion proteins, with further interest in investigating their aggregation behaviour using RT-QuiC and other biophysical techniques. Finally, we investigated the effect of glycosylation on PrP soluble and scrapie in neuronal cells.

Currently, I am working on determining the role of gangliosides on Amyloid beta 40 and 42 aggregation.

Employment

  • University of Michigan Postdoctoral Fellow
    2022 - Present
  • University of Alberta Postdoctoral Fellow
    2018 - 2019
  • Australian National University Research Assistant
    2017 - 2017

Education

  • Australian National University PhD
    2013 - 2017

Projects & Funding

Projects & funding information is unavailable.

Publications (14)