Poster Prize Winners

Phospho-proteomics analysis of human malaria parasite Plasmodium falciparum

Mahmood Alam, Lev Solaykov, Michele Graciotti, Deborah Mitcheson, Andrew Bottrill, Sharad Mistry, Christian Doerig and Andrew Tobin

Introduction

Malaria continues to kill 1-2 million people every year and most of the malaria related deaths is because of infection by Plasmodium falciparum. To develop specific drugs for malaria it is important to study the basic biology of the parasite. Protein phosphorylation is well studied regulatory mechanism in eukaryotic cells and it is being targeted to cure diseases like cancer. Despite this fact there are only few reports about phosphorylation of malaria parasite proteins. Here we have identified the phosphoproteome of late blood stage of P. falciparum parasite by mass spectrometry.

Please click here for the full abstract

Discovery and Optimisation of Novel Drug Candidates for Uncomplicated Malaria: Development and Use of Quantitative Structure Activity Relationships.

Raman Sharma,Neil G. Berry,Paul M. O’Neill,Steve A. Ward,Giancarlo A. Biagini,Nick Fisher

Robert Robinson Laboratories, Department of Chemistry, University of Liverpool.

University of Liverpool, Crown Street, Liverpool, L69 7ZD, UK

Introduction

Death and morbidity from malaria are increasing largely as a result of parasite drug resistance. There are therefore more fatalities due to malaria than 20 years ago. A solution to this problem is the discovery and development of innovative antimalarial chemotherapeutics that use novel mechanisms of action. We have recently indentified “alternative complex 1 or PfNDH2”; an enzyme in the electron transport chain (ETC) of the P. Falciparum mitochondria as potentially outstanding drug target. This enzyme is not found in the human host and inhibition of the mitochondrial function is predicted to be lethal to the asexual and liver stages of the parasite.

Please click here for the full abstract

NITD609: A new chemotype for the treatment of malaria

Bin Zou,† Bryan K. S. Yeung,† Matthias Rottmann,‡ Suresh B. Lakshminarayana,† Shi Hua Ang,† Seh Yong Leong,† Jocelyn Tan,† Josephine Wong,† Sonja Keller-Maerki,‡ Christoph Fischli, ‡ Anne Goh,† Esther K. Schmitt,¦ Philipp Krastel,¦ Eric Francotte,§ Kelli Kuhen,# David Plouffe,# Kerstin Henson,#  Trixie Wagner,§ Elizabeth A. Winzeler,# Frank Petersen,¦ Reto Brun,‡ Veronique Dartois,† Thierry T. Diagana,† and Thomas H. Keller†

†Novartis Institute for Tropical Diseases, Singapore; ‡Swiss Tropical and Public Health Institute, Basel; ¦Natural Products Unit, Novartis Pharma AG, Basel; §Novartis Institute for Biomedical Research, Basel; #Genomics Institute of the Novartis Research Foundation, San Diego

10 Biopolis Road 05-01 Chromos, Singapore 138670

Introduction

Malaria remains a persistent public health problem for about 40 percent of the global population mainly in sub–Saharan Africa. Plasmodium falciparum, the most relevant malaria parasite, is estimated to infect 300–500 million people per year and results in over one million deaths of which approximately 90% are children. Malaria control programs relying on disease prevention and artemisinin combination therapies (ACT) have been extremely effective in reducing the disease burden. However recent reports of increased tolerance to artemisinin derivatives in Plasmodium falciparum suggest that we may soon loose the last and only widely effective antimalarial drugs.

Please click here for the full abstract

Probing the Parasitic Proteome: Using ‘Click’ Probes To Investigate the Protein Targets of the Endoperoxide Antimalarials

Hanafy M. Ismail (1), Victoria E. Barton (2), Stephen A. Ward (1) and Paul M. O`Neill (2)

(1) Molecular and Biochemical Parasitology Group, Liverpool School of Tropical Medicine, Liverpool L3 5QA

(2) University of Liverpool, Department of Chemistry, Liverpool L697ZD

Introduction:

Malaria is an endemic mosquito-borne infectious disease caused by the Plasmodium parasite. The disease claims approximately one million lives every year and artemisinin-based combination therapies (ACTs) are currently the most effective treatment recommended by the World Health Organisation (WHO). Given the effectiveness of the artemisinin, the question arises, "how do these drugs kill parasites?”. After initial activation by iron they are thought to act by a number of different mechanisms however the subject remains highly controversial. The proposed mechanism of action involves the cleavage of the Endoperoxide Bridge by a source of Fe2+ or heme. This cleavage results in the formation of oxy-radicals that rearrange into primary or secondary carbon centred radicals. These radicals are proposed to alkylate proteins and form adducts with macromolecules resulting in the death of the parasite. Understanding the key proteins involved in parasite death will aid development of more effective drugs and a greater insight into how parasite cells function at a molecular level.

Please click here for the full abstract