Wellcome Centre for Integrative Parasitology

The Modrzynska Group

Current Research

Understanding the mechanisms regulating gene expression the in malaria parasite:

Malaria continues to be a major global health issue taking each year a toll of over 200 mln infections and nearly 400 thousand deaths. Importantly, the emerging resistance threatens to significantly weaken the efficiency of the current first-line antimalarial drugs and a working vaccine remains elusive. New effective approaches targeting the disease are therefore urgently needed if the eradication is to be envisaged. This, in turn, requires a better understanding of the biology of its agent –mosquito transmitted parasites from Plasmodium species.

My lab investigates one of the key processes in the parasite’s cell – gene expression regulation. Plasmodium is characterised by a very complex life cycle involving multiple life forms in both mammalian host and mosquito vector. Each transition between the life stages requires a change in expression of a large number of parasite’s genes in a short amount of time. The molecular mechanisms regulating this process, however, remain poorly understood. We are characterising the known key molecules involved in gene expression regulation and attempting to identify the new ones, employing a variety approaches, including generation of transgenic parasites, comparative genomics and next-generation sequencing technologies. While we use a number of in vitro and in vivo models to instigate different parasite’s stages the current focus of the lab is the host to vector transition– the biggest bottleneck of parasite’s life cycle and theoretically a perfect target for transmission-blocking interventions. The ultimate aim of our work is to understand how parasite rewires its gene regulatory networks at during the host change and explore these findings for therapeutic purposes.

Isabelle Fitzmaurice-O'Neill, Technician