Major Research Projects

Funding

We are funded by MRC, BBSRC, EMBO, British Council, Erasmus and Wellcome Trust.

Medical Research Council
BBSRC
Wellcome Trust

Overview

The research in the group has undertaken genome wide functional studies using rodent malaria model P. berghei to understand parasite developmental biology and the crucial novel molecules that are part of the signalling cascades, cell division, polarity during parasite development.

Major projects undertaken in the group are:

Reversible phosphorylation and sexual development in malaria parasite

Here we try to unravel the role of kinases and phosphatases in regulating parasite development and with special emphasis on their role in sexual development (gametocytes, gametes, zygotes and ookinetes). Our kinome and, more recently, our phosphatome screens identified essential regulators of mosquito transmission (Tewari et al. 2010 (: 10.1016/j.chom.2010.09.006 ); Guttery et al. 2014 (: 10.1016/j.chom.2014.05.020 )). Recent studies with phosphatase identified their crucial function in zygote development and differentiation (Guttery et al. 2012 (: 10.1371/journal.ppat.1002404 ); Patzewitz et al. 2013 (: 10.1016/j.celrep.2013.01.032 ); Guttery et al. 2014 (: 10.1016/j.chom.2014.05.020 )). Some recent reports published on this part are below:

Stage specific function of various kinases and phosphatases in mosquito stages of parasite development
Figure 1. Stage specific function of various kinases and phosphatases in mosquito stages of parasite development (Tewari et al., Cell Host & Microbe, Oct 2010 (: 10.1016/j.chom.2010.09.006 )).
Stage specific function of various phosphatases in mosquito stages of parasite development
Figure 2. Stage specific function of various phosphatases in mosquito stages of parasite development (Guttery et al., Cell Host & Microbe, 2014 (: 10.1016/j.chom.2014.05.020 )).
Role of unique plant like phosphatase PPKL in ookinete differentiation. Ookinete shows abnormal apical end in the absence of PPKL
Figure 3. Role of unique plant like phosphatase PPKL in ookinete differentiation. Ookinete shows abnormal apical end in the absence of PPKL (Guttery et al., PloS Pathogens, 2012 (: 10.1371/journal.ppat.1002404 )).
Crucial function of unique bacterial like phosphatases SHLP in ookinete differentiation
Figure 4. Crucial function of unique bacterial like phosphatases SHLP in ookinete differentiation (Patzewitz et al., Cell Reports, 2013 (: 10.1016/j.celrep.2013.01.032 )).

Understanding molecular mechanism regulating unusual cell division in malaria parasite

Our recent objective to study molecular mechanisms in plasmodial cell division identified a single homologue of cell division cycle protein CDC20 and its homologue, CDC20 homologue 1 (CDH1). By reverse genetic analyses we demonstrated that CDC20 is crucial for male gametogenesis and in its absence chromosome condensation ceases and cells fail to undergo karyokinesis and cytokinesis as shown by ultrastructure analysis below. Moreover, this study indicated that CDC20 plays an essential role in male gametogenesis but is not required for schizogony and cell multiplication at asexual stages. We are now identifying other component involved in cell division.

Cell division protein CDC20 affects male gamete formation and has absence of consensed chromatin
Figure 1. Cell division protein CDC20 affects male gamete formation and has absence of consensed chromatin (Guttery et al., PloS Pathogens, 2012 (: 10.1371/journal.ppat.1002404 )).

Polarity and cell organisation in Malaria parasite

The phylum Apicomplexa comprises over 5'000 intracellular protozoan parasites, including Plasmodium and Toxoplasma that are clinically important pathogens affecting humans and livestock. Malaria parasites belonging to genus Plasmodium possess a pellicle comprised of a plasmalemma and inner membrane complex (IMC), which is implicated in parasite motility and invasion. Recently by using live cell imaging and reverse genetics in the rodent malaria model P. berghei, we localise two unique IMC sub-compartment proteins (ISPs) and examined their role in defining apical polarity during zygote (ookinete) development (as shown below). We show that these proteins localise to the anterior apical end of the parasite where IMC organisation is initiated, and are expressed at all developmental stages, especially those that are invasive.

Two ISP genes that early marker for apical polarity in zygote development
Figure 1. Two ISP genes that early marker for apical polarity in zygote development (Poulin et al., Biology Open, 2013 (: 10.1242/bio.20136163 )).

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