Wed 24 Apr 14:00: Host manipulation by the parasite _Cryptosporidium_
Infection by the parasite Cryptosporidium is a leading cause of child mortality, no vaccine is available and the current drug treatment against this diarrheal pathogen is inefficient. The disease is transmitted through food or water contaminated with oocysts, the chlorine-resistant parasite stage. The parasite infects the epithelial cells of the small intestine in which it replicates intracellularly. Invasion and intracellular development require extensive modifications of the host cell that remain largely unknown at the molecular level. We recently showed that parasite secreted proteins play an important role in this process, however, our knowledge remains limited. Modifications of the enterocytes as well as persistent inflammation will alter the physiology of the gut and have long lasting impact on the children. In collaboration with Ross Waller laboratory, we conducted a proteomic experiment, hyperLOPIT, on fractionated Cryptosporidium sporozoites to identify the content of the various secretory organelles. This list of potential Cryptosporidium virulence factors will help fill important gaps in our knowledge of the host/parasite interplay.
- Speaker: Dr Amandine Guérin - Assistant Professor, Department of Microbiology and Molecular Medicine, University of Geneva, Switzerland
- Wednesday 24 April 2024, 14:00-15:00
- Venue: Seminar Room, Tennis Court Road, Dept of Pathology..
- Series: Parasitology Seminars; organiser: Anna Protasio.
Wed 20 Mar 14:00: Cutting back malaria: CRISPR-based approaches for antimalarial target discovery
The repeated emergence of antimalarial resistance underscores the importance of identifying new drug targets, as well as understanding the genetic architecture of current resistance pathways and any associated fitness costs. We have developed several genomics-based approaches that leverage CRISPR editing of the Plasmodium falciparum genome to validate causal resistance mutations and explore the essentiality and biological function of gene families as antimalarial targets. To more efficiently determine if compounds kill the parasite via known modes-of-action, we have generated a panel of barcoded parasite lines that encompass a wide spectrum of the known Plasmodium resistome, and have miniaturised a compound-screening assay to allow semi-automated liquid handling of parasite cultures. Competitive growth of drug-resistant lines also reveals the fitness cost of resistance. To overcome a bottleneck in evolution of resistance in the lab, we have also developed “mutator” parasite lines with an elevated mutation rate to increase the genetic complexity of parasite cultures. Finally, we are exploring whether non-coding mutations, specifically in lncRNAs, might also contribute to the parasite resistome. Collectively these approaches aim to accelerate the identification and validation of potential new targets, as well as understand the breadth of the parasite response to antimalarial challenge.
- Speaker: Professor Marcus Lee - Biological Chemistry and Drug Discovery, University of Dundee
- Wednesday 20 March 2024, 14:00-15:00
- Venue: Seminar Room, Tennis Court Road, Dept of Pathology..
- Series: Parasitology Seminars; organiser: Anna Protasio.
Wed 06 Mar 14:00: Expanding BioID: the nuclear pore complex of trypanosomes
Proximity labelling by a biotin ligase combined with mass spectrometry of biotin-affinity purified proteins (BioID) has become a powerful tool to investigate protein interactions in vivo in a range of organisms, including trypanosomes. We recently discovered an interesting off-label application of BioID for protein imaging by fluorescent streptavidin. We found streptavidin imaging superior to classical antibody labelling because it (i) provides a stronger signal with no loss in resolution (ii) can image proteins in phase-separated regions that are not accessible to antibodies and (iii) provides information on localization dynamics, since “historic” interactions are preserved. We have used the method, in combination with expansion microscopy, classical BioID, neural-network based in silico predictions and reverse genetics to reinvestigate the trypanosome nuclear pore complex.
- Speaker: Dr Susanne Kramer - Universität Wüerzburg - Germany.
- Wednesday 06 March 2024, 14:00-15:00
- Venue: Seminar Room, Tennis Court Road, Dept of Pathology..
- Series: Parasitology Seminars; organiser: Anna Protasio.
Wed 28 Feb 14:00: The complexed relationships of African Schistosoma species
Abstract not available
- Speaker: Dr Bonnie Webster - Natural History Museum - London
- Wednesday 28 February 2024, 14:00-15:00
- Venue: Seminar Room, Tennis Court Road, Dept of Pathology..
- Series: Parasitology Seminars; organiser: Anna Protasio.
Wed 07 Feb 14:00: What is still so fascinating about the trypanosome coat?
The cell surface coat of African trypanosomes has been studied for a long time. So you could assume that all the essentials are known. However, this is not the case. In my talk, I focus on the fabric from which this coat is woven (the VGSs) and their incredible dynamics. We’ve known for 20 years that the VSG coat can be recycled quickly, and we have a good idea of why. However, how the underlying biological processes can take place at such high speeds is only gradually coming to light. We’re trying to put the puzzle together step by step. In doing so, we sometimes come across surprising insights that can shed new light on basic cell biology. That’s what I’m going to tell you about. In addition, I would like to make my talk a plea for continuing research into parasitic protozoa, whose extreme adaptations can expand our reductionist perspective on cell biology.
- Speaker: Prof Markus Engstler - Universität Wüerzburg - Germany
- Wednesday 07 February 2024, 14:00-15:00
- Venue: Seminar Room, Tennis Court Road, Dept of Pathology..
- Series: Parasitology Seminars; organiser: Anna Protasio.
Wed 31 Jan 16:00: Reassessing red blood cell invasion in malaria parasites Please note 16:00 start time for this seminar
Malaria parasites rely on cycles of cellular invasion and intracellular growth to proliferate within the blood stream, a process which underpins symptoms of the disease. The cycles of cellular invasion and intracellular growthThe adaptation of P. knowlesi (Pk) to culture in human erythrocytes presents exciting opportunities to study erythrocyte invasion biology. Two major protein families have been studied extensively in P. falciparum (Pf): the erythrocyte binding-like proteins (EBPs/EBAs) and the reticulocyte binding-like proteins (RBLs/RHs). These proteins are hypothesized to have overlapping but critical roles during the invasion process. The zoonotic malaria parasite P. knowlesi, has a smaller repertoire of these proteins, and much larger and polarised invasive stages known as merozoites.
Employing a conditional knockout approach, we’ve demonstrated distinct roles for the two families at different invasion stages, including a specific role for RBL proteins in the initial identification and deformation of target host erythrocytes. Furthermore, we’ve unearthed new features that prompt a significant reassessment of invasion. Notably, we’ve discovered that Pk merozoites can engage in productive gliding motility prior to invasion, and we’ve corrected a longstanding assumption in merozoite topology – the merozoite apex is actually located in the wider end of the cell, contrary to prior beliefs. These findings unveil new aspects of this complex process and introduce fresh tools and techniques to deepen our understanding of invasion across all malaria parasite species. Finally, we will demonstrate how the new genetic tools emerging from studies in basic biology of malaria parasite can be readily adapted to facilitate vaccine, drug and diagnostics targeting a broader range of malaria parasite species.
Please note 16:00 start time for this seminar
- Speaker: Dr Robert Moon - LSHTM
- Wednesday 31 January 2024, 16:00-17:00
- Venue: Seminar Room, Tennis Court Road, Dept of Pathology..
- Series: Parasitology Seminars; organiser: Anna Protasio.
Wed 31 Jan 16:00: TBC Please note 16:00 start time for this seminar
Abstract not available
Please note 16:00 start time for this seminar
- Speaker: Dr Robert Moon - LSHTM
- Wednesday 31 January 2024, 16:00-17:00
- Venue: Seminar Room, Tennis Court Road, Dept of Pathology..
- Series: Parasitology Seminars; organiser: Anna Protasio.