Metabolomics in the fight against malaria

Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host’s metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC), a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP) malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.     

Medicinal plants in the fight against leishmaniasis

Despite the tremendous progress mode in the understanding o f the molecular biology of Leishmania and the clinical possibilities presented by some experimental chemotherapeutic agents, no new drugs have been developed for the treatment of leishmaniasis since the introduction of the pentovalent antimoniols more than 50 years ago. As reviewed here by Maurice M. Iwu, Joan E. Jackson and Brion G. Schuster, recognition of the current extensive use of herbal therapy in Leishmania-endemic regions has renewed interest in evaluation of plant remedies used in traditional medicine as sources of potential antileishmanials.     

Antimicrobial peptides: new candidates in the fight against bacterial infections

Antimicrobial peptides (AMPs) of innate origin are agents of the most ancient form of defense systems. They can be found in a wide variety of species ranging from bacteria through insects to humans. Through the course of evolution, host organisms developed arsenals of AMPs that protect them against a large variety of invading pathogens including both Gram-negative and Gram-positive bacteria. At a time of increasing bacterial resistance, AMPs have been the focus of investigation in a number of laboratories worldwide. Although recent studies show that some of the peptides are likely to have intracellular targets, the vast majority of AMPs appear to act by permeabilization of the bacterial cell membrane. Their activity and selectivity are governed by the physicochemical parameters of the peptide chains as well as the properties of the membrane system itself. In this review, we will summarize some of the recent developments that provide us with a better understanding of the mode of action of this unique family of antibacterial agents. Particular attention will be given to the determinants of AMP-lipid bilayer interactions as well as to the different pore formation mechanisms. The emphasis will be on linear AMPs but representatives of cysteine-bridged AMPs will also be discussed.     

The electronic fight against the schistosomes.

A DOS-compatible model for use on personal computers has been constructed for teaching in parasite epidemiology. The program is based on the Macdonald model of schistosome dynamics and enables simulation of the effect of a control campaign on a human worm load by reducing four transmission factors in the parasite life-cycle: (1) egg contamination, (2) snail lifetime, (3) exposure to cercariae and (4) adult worm lifetime.     

Transmission and immunity: the importance of heterogeneity in the fight against malaria

The complex relationship between transmission and parasite prevalence in humans is an important issue. Using a large dataset matching estimates of malaria transmission and Plasmodium falciparum prevalence in African children, a stimulating study published in Nature provides evidence that heterogeneity in susceptibility crucially determines the prevalence of infection. Moreover, it suggests that children who clear infections are not immune to new infections, irrespective of the amount of transmission. It is important to question the relevance of such results based on mathematical models when discussing host-parasite interactions, especially their implications for public health interventions.     

Applications of telomerase research in the fight against cancer

Telomerase, an enzyme that confers immortality upon cells and that is active in the majority of human tumors, has emerged as a powerful new marker and potential prognostic indicator and therapeutic target for cancer. Furthermore, investigations into the biology of telomerase have revealed important clues into the causes of cell death and have made progress toward answering one of the most important questions of cancer research - what gives a tumor cell an advantage over normal cells? In this article, we present the current state of telomerase research and critically assess both its potential and the pitfalls of its application in cancer diagnosis and treatment.     

Exploiting structural biology in the fight against parasitic diseases

Despite spectacular advances in structural biology over the past half-century, only approximately 2% of the structures in the Protein Data Bank are from eukaryotic parasites and less than 0.5% are from multicellular parasites. Even when only major human pathogens are considered, 3D structures of parasites are vastly underrepresented. Yet approximately one-third of the global burden of human disease comes from parasites. It is time to divert greater effort and resources in structural biology to benefit the fight against parasitic diseases. Using as leverage recent technological and methodological advances, a concerted effort to determine macromolecular structures from parasite pathogens would provide invaluable mechanistic insights on vital processes of the parasites and would suggest novel strategies for inhibiting infection.     

The fight against epizootics in the 21st Century

The fight against epizootics is today better organized. The tools, methods and strategies used work well and are constantly being improved, which is necessary since disease epidemiology is evolving extremely fast, dominated by a growing complexity associated to global changes and the emergence of new pathologies. The foundation of the strategy is still based on a permanent epidemiological surveillance and the immediate use of appropriate measures. Among the essential prerequisites there is the existence of effective veterinary services, for which support programmes have been developed, notably by the OIE, which is also responsible for the definition of the norms applicable in animal health. Three examples of control programmes against major epidemics are discussed here: Rinderpest (declared eradicated worldwide in 2011), Highly Pathogenic Avian Influenza (H5N1), and Foot and Mouth Disease.     

Androgen and estrogen receptors: potential of crystallography in the fight against cancer

Androgen (AR) and estrogen (ERalpha and ERbeta) receptors are primary targets in the treatment of hormone-sensitive tumors such as prostate or breast cancers. Because of their diverse and important roles in normal and pathologic physiology, these nuclear receptors have prompted intense research. Here, we review how structural studies conducted over the past several years on AR and ERs have provided significant advances in our comprehension of androgen and estrogen signaling and how this information can be used in the fight against cancer.