Malcolm Gardner is working in conjunction with other scientists in Seattle BioMed's Malaria Program to exploit the genome sequences of human and rodent malaria parasites to discover and validate new targets for anti-malarial drugs and vaccines. Gardner's lab is also developing new in vitro tests to determine whether experimental drugs can kill the liver stages of the malaria parasite.

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:

• 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 remnant 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.
• New in vitro tests to measure the effects of drugs on the liver stage of malaria parasites: The Plasmodium liver stage is an attractive target for drugs or vaccines because killing of the liver stage parasite prevents blood stage infection and all clinical symptoms of malaria. Despite its importance, the liver stage is the most unexplored phase in the parasite’s life cycle. The Gardner lab is developing new in vitro whole-cell assays in 96-well format to monitor the effect of drugs on liver stage parasites to speed the discovery and development of new antimalarials.
• 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., to develop new "genomes-to-antigens" methodology to enable faster identification of antigens from the human malaria parasites Plasmodium falciparum and Plasmodium vivax.
• Bioinformatics and genome annotation: Pathogen genome sequences are critical resources used by laboratory scientists to investigate pathogen biology and biochemistry and to explore how pathogens infect their hosts while avoiding the immune response. Gardner is contributing to the TriTrypDB effort and continuing work to improve the P. falciparum genome annotation.

Themes

• Plasmodium genomics and bioinformatics
• Function of the apicoplast in Plasmodium and related parasites
• Identification and validation of novel drug targets
• Development in vitro assays for malaria drug screening
• Identification of antigens for malaria vaccines and diagnostics
• Bioinformatics and genome annotation/curation.

Gardner's research is currently supported by funding from the Bill & Melinda Gates Foundation, the Medicines for Malaria Venture, the National Institute for Allergy and Infectious Diseases, the Burroughs Wellcome Fund and Seattle BioMed.