Dynamic and Combinatorial Landscape of Histone Modifications during the Intraerythrocytic Developmental Cycle of the Malaria Parasite.

A major obstacle in understanding the complex biology of the malaria parasite remains to discover how gene transcription is controlled during its life cycle. Accumulating evidence indicates that the parasite's epigenetic state plays a fundamental role in gene expression and virulence. Using a comprehensive and quantitative mass spectrometry approach, we determined the global and dynamic abundance of histones and their covalent post-transcriptional modifications throughout the intraerythrocytic developmental cycle of Plasmodium falciparum.

Ypt1/Rab1 regulates Hrr25/CK1δ kinase activity in ER-Golgi traffic and macroautophagy.

ER-derived COPII-coated vesicles are conventionally targeted to the Golgi. However, during cell stress these vesicles also become a membrane source for autophagosomes, distinct organelles that target cellular components for degradation. How the itinerary of COPII vesicles is coordinated on these pathways remains unknown.

Identifying a Rab effector on the macroautophagy pathway.

Rab GTPases are key regulators of membrane traffic. The Rab GTPase Ypt1 is essential for endoplasmic reticulum (ER)-Golgi traffic, intra-Golgi traffic, and the macroautophagy pathway. To identify effectors on the macroautophagy pathway, known autophagy-related genes (Atg genes) required for macroautophagy were tagged with GFP and screened for mislocalization in the ypt1-2 mutant.

The multifunctional autophagy pathway in the human malaria parasite, Plasmodium falciparum.

Autophagy is a catabolic pathway typically induced by nutrient starvation to recycle amino acids, but can also function in removing damaged organelles. In addition, this pathway plays a key role in eukaryotic development. To date, not much is known about the role of autophagy in apicomplexan parasites and more specifically in the human malaria parasite Plasmodium falciparum.

Pharmacokinetics, metabolism, and efficacy of the antimalarial natural product bromophycolide A.

A suite of pharmacokinetic and pharmacological studies show that bromophycolide A (), an inhibitor of drug-sensitive and drug-resistant , displays a typical small molecule profile with low toxicity and good bioavailability. Despite susceptibility to liver metabolism and a short half-life, significantly decreased parasitemia in a malaria mouse model. Combining these data with prior SAR analyses, we demonstrate the potential for future development of and its bioactive ester analogs.

High content live cell imaging for the discovery of new antimalarial marine natural products.

Background: The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies.

Post-translational modifications in Plasmodium: more than you think!

Recent evidences indicate that transcription in Plasmodium may be hard-wired and rigid, deviating from the classical model of transcriptional gene regulation. Thus, it is important that other regulatory pathways be investigated as a comprehensive effort to curb the deadly malarial parasite. Research in post-translational modifications in Plasmodium is an emerging field that may provide new venues for drug discovery and potential new insights into how parasitic protozoans regulate their life cycle.

High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery.

Background: Malaria, a major public health issue in developing nations, is responsible for more than one million deaths a year. The most lethal species, Plasmodium falciparum, causes up to 90% of fatalities. Drug resistant strains to common therapies have emerged worldwide and recent artemisinin-based combination therapy failures hasten the need for new antimalarial drugs.

Knockdown of SKN-1 and the Wnt effector TCF/POP-1 reveals differences in endomesoderm specification in C. briggsae as compared with C. elegans.

In the nematode, C. elegans, the bZIP/homeodomain transcription factor SKN-1 and the Wnt effector TCF/POP-1 are central to the maternal specification of the endomesoderm prior to gastrulation. The 8-cell stage blastomere MS is primarily a mesodermal precursor, giving rise to cells of the pharynx and body muscle among others, while its sister E clonally generates the entire endoderm (gut).