Research Jean-Claude Dujardin

Abstract

Chloroquine resistance (PvCQR) in Plasmodium vivax, the most predominant malaria species outside of Africa, is emerging globally. The mechanism and markers of PvCQR remain unknown, hampering molecular surveillance and accurate diagnosis of PvCQR. Now is the time to address PvCQR as technological advances are finally available to overcome the challenges of P. vivax research. Our hypothesis, based on our results from a clinical efficacy study in Vietnam and recently published data from P. vivax parasites adapted to a non-human primate model, is that altered gene expression of transporter genes plays a major role in PvCQR. This research aims to use transcriptomic and transgenic approaches to identify molecular markers and define the mechanism of PvCQR. By capitalizing on a large collection of P. vivax clinical samples (including CQR) and utilizing cutting-edge RNA sequencing technologies (bulk- and single-cell RNAseq), it will be possible to unravel the transcriptional network of genes underlying a PvCQR phenotype and better understand the impact of infection complexity on treatment outcome. P. knowlesi transgenic lines, differentially expressing P. vivax genes, will also be generated using CRISPR/Cas9 genome editing in order to determine drug resistance mechanisms. Outcomes of this research will directly benefit drug efficacy studies, drug resistance surveillance, and create a model suitable for industry to screen compounds for activity against PvCQR.

Researcher(s)

• Promoter: Dujardin Jean-Claude
• Fellow: Sauve Erin Louise

Research team(s)

Project type(s)

• Research Project

Abstract

Leishmania is a protozoan parasite with a remarkable tolerance for aneuploidy, while this phenomenon is often deleterious in other organisms. The result of aneuploidy is that all genes of an affected chromosome have an altered gene dosage (i.e. more or less copies) compared to the euploid situation. In Leishmania, we have previously shown that the majority of transcripts and proteins follow dosage changes in a same in vitro condition, while for the remaining products dosage compensation occurs by an unknown mechanism. This project investigates whether (i) dosage compensation occurs by alterations of transcript stability, translation efficiency and/or protein stability, driven by specific transcript and protein biomolecular features and (ii) whether dosage compensation regulation is modulated during the life cycle. As such, we will determine the relative contribution of each regulation layer to the overall compensation and establish a conceptual model of dosage compensation in Trypanosomatids. This is the first integrated multi-omic of dosage compensation in Leishmania, but also in Trypanosomatids in general. The study will lead to novel insights in how this compensation is regulated in aneuploid cells, and investigate if this has a life-stage specific component to it. These fundamental mechanisms are still incompletely understood in all eukaryotes and trough this study, we believe it is possible to gain insights in potentially hitherto unrevealed regulatory mechanisms in eukaryotes.

Researcher(s)

• Promoter: Laukens Kris
• Co-promoter: Dujardin Jean-Claude
• Fellow: Cuypers Bart

Research team(s)

• ADReM Data Lab (ADReM)

Project type(s)

• Research Project

Abstract

Sleeping sickness is caused by a unicellular parasite, the trypanosome, that is transmitted by the blood feeding tsetse fly, a species native to the African continent. When left untreated, the disease will result in coma and death. Existing therapies are limited and have serious limitations justifying the continuous search for efficient and complementary alternatives. Here, the natural transmission of the parasite through injection into the host skin by the tsetse fly is a crucial life cycle stage that has not been explored so far for targeting the parasite developmental progress in the mammalian host. The host skin is a specific micro-environment where the inoculated parasites have to survive and adapt to establish an infection and to colonize the host blood. Yet, our current knowledge of the trypanosome population and its development at this crucial early host-parasite interface is highly limited. During this project we will determine the differences in morphological and molecular properties of the early skin residing trypanosome versus other developmental stages. From this analysis we will select proteins that are specifically linked to the early skin parasite population. These proteins will be individually targeted to determine which ones are crucial for survival and development of these parasite at the biting site. This basic knowledge can eventually lead to a new strategy to prevent transmission.

Researcher(s)

• Promoter: Dujardin Jean-Claude
• Fellow: Verbeelen Margot

Research team(s)

Project type(s)

• Research Project

Abstract

This PhD project will undertake a systems biology approach to improve the understanding of Leishmania development and adaptation using a holistic view of cellular processes. As such, our goal is to stepwise unravel the complexity of the interactions between the different 'omic levels.

Researcher(s)

• Promoter: Dujardin Jean-Claude
• Co-promoter: Laukens Kris
• Fellow: Cuypers Bart

Research team(s)

Project type(s)

• Research Project

Abstract

This project aims at analyzing interactions between the intracellular parasite Leishmania and its mammalian host cell through a combination of cellular and molecular biology techniques (cell culture, in vitro infections, imaging, transcriptional profiling, proteomics and metabolomics).

Researcher(s)

• Promoter: Dujardin Jean-Claude
• Fellow: De Muylder Géraldine

Research team(s)

Project type(s)

• Research Project

Abstract

This PhD project will undertake a systems biology approach to improve the understanding of Leishmania development and adaptation using a holistic view of cellular processes. As such, our goal is to stepwise unravel the complexity of the interactions between the different 'omic levels.

Researcher(s)

• Promoter: Dujardin Jean-Claude
• Co-promoter: Laukens Kris
• Fellow: Cuypers Bart

Research team(s)

Project type(s)

• Research Project