Antimalarial drug development and new targets

The Molecular Approaches to Malaria (MAM2000) conference, Lorne, Australia, 2-5 February 2000, brought together world-class malaria research scientists. The development of new tools and technologies - transfection, DNA microarrays and proteomic analysis - and the availability of DNA sequences generated by the Malaria Genome Project, along with more classic approaches, have facilitated the identification of novel drug targets, the development of new antimalarials and the generation of a deeper understanding of the molecular mechanism(s) of drug resistance in malaria. It is hoped that combinations of these technologies could lead to strategies that enable the development of effective, efficient and affordable new drugs to overcome drug-resistant malaria, as discussed at MAM2000 and outlined here by Ian Macreadie and colleagues.     

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.     

Malaria vaccines

Although the possibility of a live attenuated malaria vaccine has been considered, current malaria vaccine development activities are dominated by attempts to develop a subunit vaccine. Hence, it is entirely appropriate that a session of the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, was devoted to vaccine development. The oral presentations in this session and the relevant poster presentations are outlined here by Robin Anders and Allan Saul.     

Pathogenesis of malaria

As the mortality rate of 20-30% for severe falciparum malaria under even the best clinical conditions testifies, access to antimalarial drugs is not sufficient to prevent an appreciable mortality from this disease. Understanding the cause of death at a cellular level is essential if additional rational treatments are to be developed. Here, Ian Clark and Louis Schofield discuss recent work presented at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, that updates the cytokine-based concept of malarial disease.     

Special issue: Cytochrome P450 structure and function: introduction

The 17th International Conference on Cytochrome P450 Biochemistry, Biophysics and Structure was held in Manchester, UK from 26-30 June 2011. This issue of FEBS J. contains review and primary research articles reflecting the breadth of science covered at this conference, and reflecting the impact of P450-related research in fields as diverse as steroid metabolism, plant biochemistry, structural biology and biotechnology.     

Traffic jams: protein transport in Plasmodium falciparum

Protein targeting in malaria parasites is a complex process, involving several cellular compartments that distinguish these cells from more familiar systems, such as yeast or mammals. At least a dozen distinct protein destinations are known. The best studied of these is the vestigial chloroplast (the apicoplast), but new tools promise rapid progress in understanding how Plasmodium falciparum and related apicomplexan parasites traffic proteins to their invasion-related organelles, and how they modify the host by trafficking proteins into its cytoplasm and plasma membrane. Here, Giel van Dooren and colleagues discuss recent insights into protein targeting via the secretory pathway in this fascinating and important system. This topic emerged as a major theme at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000.     

Plasmodium post-genomics: an update

The concept behind the first Molecular Approaches to Malaria meeting, held 1-5 February 2000 in Lorne, Australia, was ahead of its time; to convene a meeting of malaria researchers, database developers and genomics scientists, and to discuss how genomic sciences and their relevant disciplines could be applied to solve important problems in malaria research. The success of the second Molecular Approaches to Malaria meeting, held 1-5 February 2004 in the same place, together with the influence of genomics on malaria research, is testament to the vision that the organizers had at the first meeting. This review attempts to capture some of the current efforts in the post-genomics era of malaria research and highlights the approaches discussed at the Molecular Approaches to Malaria 2004 meeting.     

The Global Crisis of Malaria: Report on a Yale Conference

An international conference, “The Global Crisis of Malaria: Lessons of the Past and Future Prospects,” met at Yale University, November 7-9, 2008. The symposium was organized by Professor Frank Snowden and sponsored by the Provost’s office, the MacMillan Center, the Program in the History of Science and History of Medicine, and the Section of the History of Medicine at the Yale School of Medicine. It brought together experts on malaria from a variety of disciplines, countries, and experiences — physicians, research scientists, historians of medicine, public health officials, and representatives of several non-governmental organizations (NGOs). An underlying theme was that much could be gained from a big-picture examination across disciplinary frontiers of the contemporary public health problem caused by malaria. Particular features of the conference were its intense scrutiny of historical successes and failures in malaria control and its demonstration of the relevance of history to policy discussions in the field.     

Host cell invasion by malaria parasites

The complex life cycle of the malaria parasite includes three specialized invasive stages, distinct both in terms of their cellular architecture and in their choice of target host cell. Despite the dissimilarities between these forms, there are clear parallels in the manner by which they enter their respective host cells. Advances in the area of erythrocyte invasion by the malaria merozoite, outlined here by Chetan Chitnis and Mike Blackman and discussed at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, will undoubtedly impact on our understanding of mechanisms of cell entry by the other invasive forms. Similarly, recent progress in dissecting the functional role of surface proteins expressed by sporozoite and ookinete stages has provided fascinating insights into general aspects of invasion by all invasive stages of apicomplexan parasites.     

Focus on Plasmodium vivax

In Bangkok, Thailand, 3-8 February 2002, the Multilateral Initiative on Malaria convened the first malaria conference, Vivax Malaria Research: 2002 and Beyond, devoted entirely to Plasmodium vivax research.     

Signal peptide cleavage site prediction

A series of reports - and extracts of reports - from the Freedom of Information Conference, 6-7 July, 2000, New York Academy of Medicine. The conference was sponsored by BioMed Central, to promote debate about the communication and validation of biomedical research published on the internet. Details of the meeting and all presentations are available in full online at http://biomedcentral.com/info/conference.asp

     

Varieties of modules: kinds, levels, origins, and behaviors

This article began as a review of a conference, organized by Gerhard Schlosser, entitled "Modularity in Development and Evolution." The conference was held at, and sponsored by, the Hanse Wissenschaftskolleg in Delmenhorst, Germany in May, 2000. The article subsequently metamorphosed into a literature and concept review as well as an analysis of the differences in current perspectives on modularity. Consequently, I refer to general aspects of the conference but do not review particular presentations. I divide modules into three kinds: structural, developmental, and physiological. Every module fulfills none, one, or multiple functional roles. Two further orthogonal distinctions are important in this context: module-kinds versus module-variants-of-a-kind and reproducer versus nonreproducer modules. I review criteria for individuation of modules and mechanisms for the phylogenetic origin of modularity. I discuss conceptual and methodological differences between developmental and evolutionary biologists, in particular the difference between integration and competition perspectives on individualization and modular behavior. The variety in views regarding modularity presents challenges that require resolution in order to attain a comprehensive, rather than a piecemeal and fragmentary, evolutionary developmental biology. J. Exp. Zool. (Mol. Dev. Evol.) 291:116-129, 2001.     

Malaria vaccines: if at first you don't succeed..

The Roll Back Malaria campaign vowed to halve the global burden of malaria in ten years but, midway into that campaign, few new malaria control tools have been introduced, and many established methods appear to be failing with effective chemotherapy being perhaps the most problematic. It has been repeatedly argued that the discovery and implementation of a safe and effective vaccine against malaria is a major priority in the control of the disease. Indeed, many malaria control experts believe that sustainable reductions in malaria control will be nigh on impossible in the absence of such a vaccine. While most would agree that we are still some way from being able to introduce a vaccine, steady progress is being made. We review here some new approaches and developments in vaccine research that were discussed at the Molecular Approaches to Malaria conference held 1-5 February 2004 in Lorne, Australia.     

Overlooked post-translational modifications of proteins in Plasmodium falciparum: N- and O-glycosylation -- a review

Human malignant malaria is caused by Plasmodium falciparum and accounts for almost 900,000 deaths per year, the majority of which are children and pregnant women in developing countries. There has been significant effort to understand the biology of P. falciparum and its interactions with the host. However, these studies are hindered because several aspects of parasite biology remain controversial, such as N- and O-glycosylation. This review describes work that has been done to elucidate protein glycosylation in P. falciparum and it focuses on describing biochemical evidence for N- and O-glycosylation. Although there has been significant work in this field, these aspects of parasite biochemistry need to be explored further.     

The biological standard of living in Indonesia during the 20th century: Evidence from the age at menarche

This article analyses long-term changes in the mean age at menarche (MAM) as a biological indicator of changes in the standard of living in Indonesia. It finds that MAM was about 15.5 for birth cohorts in the late-19th century, decreasing to 14.5 by the 1930s, at which level it stagnated until the gradual decrease resumed since the early 1960s to around 12.5 in the mid-2000s. The article considers that long-term improvements in nutrition, educational attainment and health care explain these trends. An international comparison of long-term changes finds that MAM in Indonesia was much lower than in Korea and China until respectively 1970 and 1990, but comparable to Japan until 1950 and to Malaysia until 1930. The article presents reasons why these differences are unlikely to be related to dissimilarities in climate and ethnicity, and concludes that they are indicative of relative standards of living.     

Comments on the International Symposium on Light,Endocrine Systems and Cancer

A conference was held at the University of Cologne on May 2-3, 2002, to discuss the strength-of-the-evidence supporting a linkage between light, endocrine systems and cancer. This overview of the conference is intended to summarize some of the key elements of the conference and to indicate both conclusions and research gaps identified by this reviewer.     

The United States Army and malaria control in World War II

The United States Army faced difficult malaria control problems both at home and abroad during World War II. This challenge forced the Army to develop new tools and strategies for use in malarious areas where fighting was occurring. Due to the severe malaria problems being faced in some combat areas and the need to solve these problems quickly, intensive malaria research and operational programs were developed and implemented. With these concerted efforts and the simultaneous development of new control technologies, malaria was successfully controlled in most locations. In order to accomplish this high level of control both in the US and overseas, the Army developed a very organized approach to the malaria problem and implemented it in an effective manner. The creation of new technical solutions was also strongly emphasized and out of this effort came the development of effective antimalaria drugs to replace quinine, of new insecticides and of more effective systems for delivering these insecticides. Some of the major new tools which came out of this research were DDT and drugs such as Atabrine and chloroquine. The availability of Atabrine and DDT revolutionized malaria control throughout the world. The knowledge and experience gained through the use of these new tools by the US Army and other agencies in World War II provided the basis for a new optimism regarding malaria control which then led to the development of the global malaria eradication strategy in the post-war years.     

Protective immunity to pre-erythrocytic stage malaria

The development of a vaccine against malaria is a major research priority given the burden of disease, death and economic loss inflicted upon the tropical world by this parasite. Despite decades of effort, however, a vaccine remains elusive. The best candidate is a subunit vaccine termed RTS,S but this provides only partial protection against clinical disease. This review examines what is known about protective immunity against pre-erythrocytic stage malaria by considering the humoral and T cell-mediated immune responses that are induced by attenuated sporozoites and by the RTS,S vaccine. On the basis of these observations a set of research priorities are defined that are crucial for the development of a vaccine capable of inducing long-lasting and high-grade protection against malaria.     

New methods to approach immunotherapy of cancer – and strategies of tumours to avoid elimination

Owing to the intense effort of numerous investigators, the number of tumour antigens potentially of use for clinical immunotherapy continues to increase. At the same time, further strategies employed by tumour cells to avoid destruction by the immune system are being uncovered. A combined onslaught to target tumour cells and prevent their “escape” will be required for successful immunotherapy. Progress in this area was the subject of a meeting supported by the European Cancer Research Consortium “EUCAPS”, which was held in London in February 2000. This conference was the second of a series, the first of which was summarised previously in this journal [Pawelec G et al. (1999) Cancer Immunol Immunother 48: 214]. Received: 14 March 2000 / Accepted: 30 March 2000     

Selected papers from the Fourth Annual q-bio Conference on Cellular Information Processing

This special issue consists of 11 original papers that elaborate on work presented at the Fourth Annual q-bio Conference on Cellular Information Processing, which was held on the campus of St John's College in Santa Fe, New Mexico, USA, 11-14 August 2010. Now in its fourth year, the q-bio conference has changed considerably over time. It is now well established and a major event in systems biology. The 2010 conference saw attendees from all continents (except Antarctica!) sharing novel results and participating in lively discussions at both the oral and poster sessions. The conference was oversubscribed and grew to 27 contributed talks, 16 poster spotlights and 137 contributed posters. We deliberately decreased the number of invited speakers to 21 to leave more space for contributed presentations, and the attendee feedback confirmed that the choice was a success. Although the q-bio conference has grown and matured, it has remained true to the original goal of being an intimate and dynamic event that brings together modeling, theory and quantitative experimentation for the study of cell regulation and information processing. Funded in part by a grant from NIGMS and by DOE funds through the Los Alamos National Laboratory Directed Research and Development program, the conference has continued to exhibit youth and vigor by attracting (and partially supporting) over 100 undergraduate, graduate and postdoctoral researchers. The associated q-bio summer school, which precedes the conference each year, further emphasizes the development of junior scientists and makes q-bio a singular event in its impact on the future of quantitative biology. In addition to an increased international presence, the conference has notably diversified its demographic representation within the USA, including increased participation from the southeastern corner of the country. One big change in the conference this year is our new publication partner, Physical Biology. Although we are very grateful to our previous partner, IET Systems Biology, for their help over the years in publicizing the work presented at the conference, we felt that the changing needs of our participants required that we find a new partner. We are thrilled that Physical Biology is publishing the q-bio proceedings this year. It has been a great collaboration, as evidenced by the high quality of this special issue. What's next for q-bio? We are happy to report that NIGMS has recently extended the q-bio conference grant for the next three years, ensuring strong support for junior researchers who need financial assistance to participate in the event. The conference will retain its emphasis on cellular information processing, but will also build connections to other areas of modern biology and biotechnology, focusing specifically on ecology and evolutionary biology next year. Indeed, to fully understand biological information processing systems, they must be studied in their ecological contexts. We will continue to honor distinguished contributors to the field in our opening banquets; the tradition started with Howard Berg, Bruce Alberts and Michael Savageau in previous years, and continues with Dennis Bray at the upcoming 2011 event. Starting in 2011, the conference will also venture into exploration of the social aspects of science. The future is bright for q-bio! We will see you at the Fifth Annual q-bio Conference on 10-13 August 2011, in Santa Fe, New Mexico, USA and at the Sixth Annual q-bio Conference in early August 2012.