Molecular approaches to malaria: seeking the whole picture

This year, Australia hosted its first major international conference on malaria - Molecular Approaches to Malaria in Lorne, Victoria, 2-5 February 2000 (MAM2000). The worldwide research effort toward a better understanding of the pathogenesis and control of malaria in the post-genomic era was discussed and debated by over 250 researchers from 18 countries during four days packed with molecular biology, cell biology, genomics, vaccines and pathogenic mechanisms. This special malaria edition of Parasitology Today is an attempt to capture and summarize the quality and breadth of work presented at the conference and place this in the context of the current global malaria research effort; eight of the nine Reviews in this issue have been written by session chairs or presenters at MAM2000.     

Molecular approaches to malaria: MAM 2004 and beyond

This special issue of Trends in Parasitology comprises a collection of timely reviews arising from the 2nd Molecular Approaches to Malaria meeting held 1-5 February 2004 in Lorne, Australia, four years after the successful inaugural meeting. As the name suggests, Molecular Approaches to Malaria focused on the latest molecular developments in malaria research, and their biological and clinical implications. By no means is this special issue intended to represent a comprehensive recapitulation of all of the presentations at the meeting. Rather, the articles address, in more general terms, recent advances on broader themes that were prominent at Molecular Approaches to Malaria meeting 2004.     

Molecular approaches to field studies of malaria

The third 'Molecular Approaches to Malaria' conference was held in Lorne, Australia, in February 2008 and provided extensive information on the application of molecular tools in field studies on malaria. In recent years, technological advances and capacity building in malaria-endemic countries have permitted molecular tools to be applied much more frequently and successfully with exciting new findings. In this review, Hans-Peter Beck and Kevin Tetteh report on the most recent findings using molecular tools in field studies.     

Molecular approaches to epidemiology and clinical aspects of malaria

Malaria is a problem of global importance, responsible for 1-2 million deaths per year, mainly in African children, as well as considerable morbidity manifested as severe anaemia and encephalopathy in young children. Fundamental to the development of new tools for malaria control in humans is an increased understanding of key features of malaria infection, such as the diversity of outcome in different individuals, the understanding of different manifestations of the disease and of the mechanisms of immunity that allow clinical protection in the face of ongoing low-grade infection (concomitant immunity or premunition). Here, Graham Brown and colleagues review some of the ways in which molecular approaches might be used to increase our understanding of the epidemiology and clinical manifestations of malaria, as discussed at the Molecular Approaches to Malaria conference (MAM2000), Lorne, Australia, 2-5 February 2000.     

DNA vaccine against malaria: a long way to go

Vaccination is the attempt to mimic certain aspects of an infection for the purpose of causing an immune response that will protect the individual from that infection. Malaria, a disease responsible for immense human suffering, is caused by infection with Plasmodium spp. parasites, which have a very complex life cycle--antigenically unique stages infect different tissues of the body. It is a parasitic disease for which no successful vaccine has been developed so far, despite considerable efforts to develop a subunit vaccine that offers protective immunity. Due to the spread of drug-resistant malaria, efforts to develop an effective vaccine have become increasingly critical. DNA vaccination provides a stable and long-lived source of protein vaccine capable of inducing both antibody- and cell-mediated immune responses to a wide variety of antigens. Injected DNA enters the cells of the host and makes the protein, which triggers the immune response. According to present needs, the flexibility of DNA vaccine technology permits the combination of multiple antigens from both the preerythrocytic and erythrocytic stages of malaria parasite. DNA vaccines with genes coding for different antigenic parts of malaria proteins have been created and presently some of these are undergoing field trials. The results from these trials will help to determine the likelihood of success of this technology in humans. This review presents an update of the studies carried out in malaria using DNA vaccine approach, the challenges, and the future prospects.     

Molecular approaches to contraceptive development

The next generation of contraceptives will be based on the identification of novel molecules essential for reproductive processes and will rely on the refinement of older as well as newer technologies. Functional analysis of naturally occurring reproductive genetic disorders and creation of mice null for specific genes would greatly assist in the choice of genetic targets for contraceptive development. Structure-based design of drugs as exemplified by the preparation of an orally active non-peptide gonadotropin releasing hormone (GnRH) would revolutionize drug formulation and delivery for a peptide analogue. This review examines some of the molecular targets that may change contraceptive choices in the future.     

Molecular approaches to nerve regeneration.

Current research into regeneration of the nervous system has focused on defining the molecular events that occur during regeneration. One well-characterized system for studying nerve regeneration is the sciatic nerve of rat. Numerous studies have characterized the sequence of events that occur after a crush injury to the sciatic nerve (Cajal 1928; Hall 1989). These events include axon and myelin breakdown, changes in the permeability of the blood vessels, proliferation of Schwann cells, invasion of macrophages, and the phagocytosis of myelin fragments by Schwann cells and macrophages. The distal segment of the injured sciatic nerve provides a supportive environment for the regeneration of the nerve fibres (Cajal 1928; David & Aguayo 1981). Within a period of weeks, the injured sciatic nerve is able to regrow and successfully reinnervate the appropriate targets. Some of the molecules that provide trophic support for the regrowing nerve fibres have been identified, including nerve growth factor (NGF) (Heumann et al. 1987) and glial maturation factor beta (Bosch et al. 1989). Another class of molecules show changes in their rates of synthesis during regeneration, including both proteins (Skene & Shooter 1983; Muller et al. 1986) and mRNA species (Trapp et al. 1988; Meier et al. 1989). To better understand nerve regeneration, we have taken two, parallel molecular approaches to study the events associated with regeneration. The first of these is to study in detail the mechanism of action of a molecule that has been implicated in the regeneration process, nerve growth factor. The second approach is to identify novel gene sequences which are regulated during regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular approaches to the study of myiasis-causing larvae

Among arthropod diseases affecting animals, larval infections - myiases - of domestic and wild animals have been considered important since ancient times. Besides the significant economic losses to livestock worldwide, myiasis-causing larvae have attracted the attention of scientists because some parasitise humans and are of interest in forensic entomology. In the past two decades, the biology, epidemiology, immunology, immunodiagnosis and control methods of myiasis-causing larvae have been focused on and more recently the number of molecular studies have also begun to increase. The 'new technologies' (i.e. molecular biology) are being used to study taxonomy, phylogenesis, molecular identification, diagnosis (recombinant antigens) and vaccination strategies. In particular, more in depth molecular studies have now been performed on Sarcophagidae, Calliphoridae and flies of the Oestridae sister group. This review discusses the most topical issues and recent studies on myiasis-causing larvae using molecular approaches. In the first part, PCR-based techniques and the genes that have already been analysed, or are potentially useful for the molecular phylogenesis and identification of myiasis-causing larvae, are described. The second section deals with the more recent advances concerning taxonomy, phylogenetics, population studies, molecular identification, diagnosis and vaccination.     

Molecular biological approaches to plant nutrition

In the last decade, understanding of ion transport has grown sufficiently to pose sensible questions about the molecular nature of the processes and their regulation. Techniques for identifying and cloning genes and for genetic transformation provide the means for answering these questions.Transport of ions across membranes is obviously a major aspect of mineral nutrition since it occurs during initial absorption, compartmentation and mobilisation of nutrients. Here, we will briefly review the types of transport protein involved and show how molecular biology and recombinant DNA technology have revealed something of their structure. Strategies used to identify the genes for transporters are discussed and reference is made to areas in which the availability of cloned genes will facilitate future studies.Mineral nutrition involves, however, more than membrane transport. The absorption rates of major nutrients are quite strictly regulated by biochemical factors which vary with the rate at which nutrients are used in growth. Nitrogen, sulphur and phosphate nutrition in micro-organisms are regulated by the interaction of various DNA-binding proteins with the promoter regions of genes for key enzymes in the assimilatory pathways and the specific ion permeases. The expression of the regulatory protein or its activity can be modified by metabolites, such as glutamine. Some evidence supports the idea that higher plants also have groups of genes with a common regulation of expression.An attempt is made to identify some reasonable objectives, which should increase understanding of the regulation of nutrient transport.Abbreviations and conventions cDNA complementary strand of DNA prepared from a messenger RNA - NR nitrate reductase - NiR nitrite reductase - P_i inorganic phosphate - PPase pyrophosphate - RUBISCO rubulose bisphosphate carboxylase oxygenase. Genes are referred to as follows e.g. cys-3 and scon-1. The protein products of these genes, where they have no familiar name are referred to as CYS3 and SCON-1 respectively     

Molecular approaches to understanding mycorrhizal symbioses

Molecular analyses of plant–microbe interactions have become common place in the last two decades. Although there are philosophical considerations about the application of a reductionist approach to some areas of research, the collaborative interface (e.g. molecular ecology) can provide specialised insight to the generalist, whilst adding broader relevance to the research of the specialist. However, the expense of this discipline has tended to restrict research to work on model host–microbe interactions. Molecular techniques were embraced early on by a few pioneers from the field of mycorrhizal research. Despite some high profile research, the number of molecular mycorrhizal publications has only recently begun to escalate. However the extent of literature now has exceeded the capacity for a comprehensive short review. In this paper we will briefly discuss the use of model species for molecular research and explore the range of questions that are being addressed using molecular techniques, whilst minimising use of specific jargon, to maximise the usefulness of this review to a non specialist audience. Our primary focus is on arbuscular mycorrhizal symbiosis, to complement the papers by Tagu et al., Podila et al. and Chalot et al. (all this volume), who have addressed aspects of research on ectomycorrhizal symbioses. Here we include specific citations from research groups around the world, along with reference to more detailed reviews, to provide a taste of the current excitement in this fundamental and rapidly evolving research field.     

Molecular genetic approaches to understanding the actin cytoskeleton

New tools in molecular genetics, such as genetic interaction screens and conditional gene targeting, have advanced the study of actin dynamics in a number of model systems. Yeast, Dictyostelium, Caenorhabditis elegans, Drosophila, and mice have contributed much in recent years to a better understanding of both the numerous functions and modes of regulation of the actin cytoskeleton.     

Molecular simulation approaches to membrane proteins

Molecular simulations are an invaluable tool for understanding membrane proteins. Improvements to both hardware and simulation methods have allowed access to physiologically relevant timescales and have permitted the simulation of large multimeric complexes. This, coupled to the recent expansion in membrane protein structures, provides a means to elucidate the relationship between protein structure and function. In this review, we discuss the progress in using simulations to understand the complex processes that occur at the boundary of a cell, ranging from the transport of solutes and the interactions of ligands with ion channels to the conformational rearrangements required for gating of channels and the signaling by membrane-associated complexes.