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Pegine Walrad is an Anniversary Research Lecturer in Molecular Parasitology appointed to the Department of Biology in celebration of the University of York’s 50th Anniversary and a member of the Centre for Immunology and Infection. Training originally as a zoologist at Michigan State University (BSc) and veterinary nurse (NC, USA), Pegine developed research interests in pathology, molecular biology, and developmental genetics during her PhD working on flies and yeast at Stony Brook University, NY. Pegine shifted fields to molecular parasitology when she secured a Wellcome Trust-funded Post Doctoral position examining developmental regulators of the Trypanosoma brucei lifecycle at the University of Edinburgh. She is currently developing her independent research career in Leishmania spp. parasitology at the University of York and was recently awarded a prestigious New Investigator Research Grant by the MRC to pursue trans-regulators of Leishmania spp. differentiation to human-infectious forms.
Michigan State University
Stony Brook University, NY
University of York
Pegine’s laboratory works on kinetoplastid parasites which cause human disease worldwide; afflicting the poorest of society. The Leishmaniases currently infect 12 million people with 2 million new cases annually. It is the second biggest killer of parasitic diseases and 70% of those infected are under 15yrs old. No vaccine exists, available treatments have toxic side effects and resistance to existing treatments is on the rise.
Research centers on regulators of Leishmania parasite differentiation that enable human leukocyte infection, with emphasis on post-transcriptional control as the primary mode of gene regulation. Leishmania parasites infect distinct host environments and this requires concise and responsive adaptation to survive. Gene regulators and signaling pathways that initiate parasite response to host cells and enable adaptation have yet to be identified and are key to combating the diseases caused by these parasites. Regulatory systems enabling parasite development are characterized using a combination of molecular, biochemical, genetic and bioinformatic techniques, utilising transcriptomic and proteomic approaches to isolate human-infectious stage specific regulators.
2014 Lab Members
Current MRC New Investigator Research Grant:
PI, “Identifying and Characterising Developmental regulators of Infective Leishmania spp. “ 10/2013 - 03/2017
1. Investigating the molecular machinery that controls autophagy during Leishmania spp. differentiation. (Joint Supervision with Prof. Nia Bryant)
Central to eukaryotic cellular differentiation is the tightly regulated membrane trafficking pathway of autophagy, (literally self-eating); originally characterised as a defense against starvation conditions, more recently shown to be required for cellular development. The Bryant lab has identified an interaction between the yeast SNARE proteins and effector proteins as key regulators of autophagy: disruption of these interactions blocks autophagy. Autophagy is essential for lifecycle progression of many unicellular eukaryotic pathogens including Leishmania spp., but the mechanisms involved are largely uncharacterized. In silico analyses from the Walrad lab has identified the Leishmania orthologues of implicit factors and we hypothesise that these autophagy-implicit factors represent good therapeutic targets to prevent Leishmania spp. differentiation into mammalian infectious form(s).
To test the above hypothesis the aims of this project are to create and ectopically express molecules in Leishmania spp. orthologous to those the Bryant lab developed in yeast. The student will assess the consequences of this on Leishmania differentiation.
The project will provide experience in a wide range of techniques including molecular biology, immunoblot analysis, confocal microscopy and category 3 cell culture.
2. Investigating motility parameters and molecules that impact Leishmania spp. infectivity (Joint Supervision with Dr. Laurence Wilson)
Motility is essential for parasite survival during transitions between different hosts and enables lifecycle progression. In the malaria-causing parasite Plasmodium berghei, the molecules governing sporozoite motility and infectivity are tightly linked. Motility is also necessary for parasite reproduction and viability in the Sleeping Sickness-causing parasite Trypanosoma brucei. Central to Leishmania spp. parasite infectivity is their ability to swim to human immune cells, but details of the swimming behaviour and participating biomolecules remain obscure.
The Walrad and Wilson labs are well placed to examine the role of motility in Leishmania spp. infectivity, given their complementary expertise in molecular parasitology and parasite motility investigations. Proof of concept holographic image data has already been obtained from cells of Leishmania mexicana, and an array of techniques aimed at high-throughput motility analyses have been developed for other species. This project will require significant further development of both image analysis streams.
We hypothesise that a study of biophysical swimming parameters and biomolecular factors would reveal good therapeutic targets for preventing Leishmania spp. invading immune cells and/or differentiating into mammalian infectious form(s).
The project will provide experience in a wide range of techniques including molecular biology, immunoblot analysis, holographic and confocal microscopy, digital image analysis and category 3 cell culture.