Chromatin structure and epigenetics in Plasmodium falciparum

 The genome of the malaria parasite Plasmodium falciparum is maintained primarily as transcriptionally competent, euchromatin with only restricted islands of transcriptionally silent, condensed heterochromatin. The paradigm for heterochromatin function is the regulation of development and P. falciparum does use heterochromatin to silence several genes critical for developmental transitions. However, most of the P. falciparum genes selectively silenced by heterochromatin are members of contingency gene families expressed in asexual parasites. By clonally variant, stochastic activation of these genes P. falciparum can rapidly generate progeny heritably expressing different variants of a single gene family that each encode different phenotypes. This strategy obviates the need for complex signalling pathways to induce specific contingency genes. The phenotypic plasticity thus conferred on the parasite also enables it to adapt far more rapidly to an altered host environment than could be achieved by random mutation. This process of epigenetic regulation is dependent on chromatin structure. Chromatin also plays a critical role in the non-epigenetic, cyclical regulation of gene expression in every generation. The unique nature of some of the P. falciparum chromatin associated factors suggests they could be useful drug targets.

Dr Michael Duffy is a Senior Research Fellow at the School of Biosciences, Bio21 Institute, The University of Melbourne. He did his PhD in microbiology at the School of Veterinary Science, University of Melbourne, and then post-doctoral research into Plasmodium falciparum for the Walter and Eliza Hall Institute, but based at the Eijkman Institute in Jakarta Indonesia. He returned to University of Melbourne where his research has focussed on how elements of chromatin structure regulate gene expression in the malaria parasite Plasmodium falciparum. This work developed through his study of the epigenetic control of antigenic variation in P. falciparum and has diversified into the broader study of unique chromatin proteins in P. falciparum, including variant histones and bromodomain proteins. The latter are of particular interest as potential therapeutic targets.