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Malcolm Gardner, Ph.D.
Mission
At SBRI, Dr. Gardner is working in conjunction
with other scientists in the 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. His 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 SBRI, Dr. 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. Dr.
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. We are 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. Dr. Gardner is collaborating with
Dr. Ruobing Wang 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. Dr. Gardner is contributing to the
TriTrypDB effort and continuing work to
improve the P. falciparum genome
annotation.
Themes
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Plasmodium genomics and bioinformatics
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Function of the apicoplast in
Plasmodium and related
parasites
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Identification and validation of novel drug targets
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Development in vitro
assays for malaria drug screening
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Identification of antigens for malaria vaccines and
diagnostics
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Bioinformatics and genome annotation/curation.
Laboratory Accomplishments
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Identified a potential drug target in the
Plasmodium apicoplast
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Coordinated the analysis and publication of the
P. falciparum
genome sequence
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Directed the
sequencing and annotation of 4 P.
falciparum chromosomes
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Sequenced the genomes of the human fungal pathogen
Coccidioides posadasii and the African cattle parasite Theileria parva
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Sequenced the genome of the host-cell transforming
cattle parasite Theileria parva
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Generated ESTs and BAC-end sequences for the
Anopheles gambiae genome project
Dr. 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 SBRI.
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