Malcolm Gardner is working in conjunction with other scientists in Seattle BioMed's Malaria Program and the University of Washington to exploit the genome sequences of human and rodent malaria parasites to discover and validate new targets for anti-malarial drugs and vaccines. He is also collaborating with the Aderem Lab to investigate the immune responses and gene expression patterns in the peripheral blood of volunteers parricipating in clinical trials of experimental vaccines. The goal is to identify immune signatures that are generated early after immunization that predict protection against malaria infection. These protective signatures could then guide the development of more effective vaccines.
Research
Prior to joining the Institute, Gardner led efforts at The Institute for Genomic Research (TIGR; now the J Craig Venter Institute) to sequence the genomes of the human malaria parasite Plasmodium falciparum, the related cattle parasite Theileria parva, and the human pathogenic fungus Coccidioides posadasii. He is now directing his efforts toward hypothesis-driven research using a mixture of molecular, biochemical, cell biological, and high throughput approaches including genomics, functional genomics, proteomics and bioinformatics. His areas of research include:
- Systems vaccinology: An effective malaria vaccine that protects both children and adults will be a critical tool for malaria eradication. Recent field trials in Africa of an experimental vaccine have been very encouraging, but vaccine development is a long, laborious process. Other malaria vaccines are being studied in both animal models and in clinical trials. Gardner, in collaboration with the Aderem Lab and others, is employing systems biological approaches to analyze immune responses and gene expression patterns induced by vaccination that can predict protective efficacy and guide further research to produce more effective next-generation malaria vaccines.
- Identification and characterization of novel antigens in Plasmodium and other intracellular pathogens: While the P. falciparum genome sequence has been instrumental for the identification of new drug targets, less progress has been made towards the identification of novel vaccine antigens, in part due to the lack of high throughput in vitro systems for the identification of antigens that are targets of protective humoral or cellular immune responses. Gardner is collaborating with Seattle BioMed's Ruobing Wang, Ph.D., and Antigen Discovery, Inc. to develop new "genomes-to-antigens" methodology to enable faster identification of antigens from the human malaria parasites Plasmodium falciparum and Plasmodium vivax.
- Function of the apicoplast in the malaria parasite and related organisms: The malaria parasite Plasmodium and related parasites such as Toxoplasma and Theileria contain an organelle called the apicoplast, a plastid-like structure left over from an ancient secondary endosymbiotic event. Many studies have shown that the apicoplast is required for parasite replication and that malaria parasites can be killed by drugs that inhibit apicoplast functions. Gardner is combining comparative genomics with laboratory studies to investigate the functions of apicoplast proteins in order to identify and validate new drug targets. His lab recently completed biochemical analyses of an apicoplast tRNA synthetase that is needed for protein biosynthesis.
Themes
- Plasmodium genomics and bioinformatics
- Systems vaccinology to identify early immune responses that correlate with and predict immunogenicity and protection in clinical trials of candidate malaria vaccines
- Identification of antigens for malaria vaccines and diagnostics
- Function of the apicoplast in Plasmodium and related parasites
- Identification and validation of novel drug targets
Gardner's research is currently supported by funding from PATH/MVI and Seattle BioMed.
Biography
Education
Ph.D. Biochemistry University of Tennessee
Oak Ridge Graduate School of Biomedical Sciences, Biology Division,
Oak Ridge National Laboratory, Oak Ridge, TN
B.S. Honors Biology Dickinson College, Carlisle, PA
Professional Experience
- Full Professor, Seattle Biomedical Research Institute, 2005 – Present
- Affiliate Professor, Department of Global Health, University of Washington, Seattle, WA, 2009 - Present
- Investigator, Parasite Genomics Group, The Institute for Genomic Research, Rockville, MD, 2003-2005
- Associate Investigator, Parasite Genomics Group, The Institute for Genomics Research, Rockville, MD, 1999 - 2003
- Assistant Investigator, Department of Eukaryotic Genomics, The Institute for Genomic Research, Rockville, MD, 1997 - 1999
- Research Assistant Professor, Department of Microbiology and Immunology, University of Maryland at Baltimore, Baltimore, MD, 1995 - 1997
- Senior Molecular Biologist, Malaria Program, Naval Medical Research Institute, Rockville, MD, 1993-1997
- National Research Council Senior Fellow, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC, 1991-1993
- Postdoctoral Fellow, Division of Parasitology, National Institute for Medical Research, London, England, 1985-1991
Select Honors and Awards
- Letters of Commendation (2), Naval Medical Research Institute, 1996-1997
- National Research Council Senior Fellow,1991
- National Research Service Award, 1981
Field of Study
I entered the malaria field as a postdoc at the National Institute for Medical Research in London, drawn by the realization that malaria was a tremendously important but relatively under-studied disease. I thought that there was a great deal yet to be learned about the parasite at the molecular level. I subsequently had a "once-in-a-lifetime" opportunity to participate in the Plasmodium falciparum genome project while working at The Institute for Genome Research. The genome sequence that was determined with our partners at the Wellcome Trust Sanger Institute, Stanford University, and the Naval Medical Research Center is being used by scientists worldwide to accelerate malaria research and to identify new drug and vaccine targets for malaria.
At Seattle BioMed, I am extending my previous work in genomics via laboratory-based investigations to learn more about the apicoplast, an essential organelle in malaria parasites that contains novel drug targets. We are currently evaluating a new target, the indirect aminoacylation pathway, which we identified via comparative genomics approaches. My lab is also working with the Wang Lab and Antigen Discovery, Inc. to identify new antigens that could be used in malaria vaccines or for diagnostics. We also started a new collaboration with the Aderem Lab at Seattle BioMed and the Emory Vaccine Center to use systems biology approaches to identify immune signatures in volunteers receiving experimental malaria vaccines that may predict vaccine efficacy (funded in whole or in part by the PATH Malaria Vaccine Initiative). We welcome the opportunity to mentor the next generation of malaria researchers.
Staff
Boniface Mailu, Postdoctoral Scientist
