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Michael E. Grigg, Ph.D.
Building 4, Room B1-06
4 Memorial Drive
Bethesda, MD 20892-0425
Phone: 301-402-1609
Fax: 301-402-0079
griggm@niaid.nih.gov

Laboratory of Parasitic Diseases

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Michael E. Grigg, Ph.D.

Photo of Michael E. Grigg, Ph.D.

Chief, Molecular Parasitology Unit, LPD

Major Areas of Research

  • Biology and genetics of virulence shifts in protozoan parasite populations
  • Forward/reverse genetics and functional genomic screens that identify protozoan parasite virulence factors
  • Mechanisms of host resistance and Toxoplasma pathogenesis
  • Structure-function and regulation analyses of parasite gene families that modulate host immunity, infectivity, and parasite transmissibility
 

Program Description

Parasitic protozoa are serious pathogens of humans and animals throughout the world whose biology is quite remarkable. Studies investigating their cell and molecular biology have identified unique paradigms of eukaryotic pathogenesis, including antigenic variation, virulence shifts, and RNA editing. The primary goal of the Molecular Parasitology Unit is to understand the molecular basis ofvirulence and pathogenesis in a class of parasitic protozoa known as the Apicomplexa.

Our research is focused primarily on the food- and water-borne parasite, Toxoplasma gondii, a serious pathogen capable of causing lethal infections in the developing fetus and in immunocompromised patients, as well as blinding chorioretinitis in both children and adults. In all hosts, Toxoplasma establishes long-term chronic infections that persist for life despite the induction of strong immunity. Eliminating the ability of the parasite to evade sterilizing immunity is central to controlling both its propagation and pathogenesis, as no vaccine or drug is currently capable of doing this. And despite its prevalence and importance as a human pathogen, surprisingly little is known about how Toxoplasma causes disease.

Our three-pronged research approach involves: 1) investigating the genetic basis of virulence shifts caused via sexual recombination in parasitic protozoa using Toxoplasma gondii as the genetic model; 2) determining the molecular interactions that control Toxoplasma pathogenesis in a naturally infectious, murine disease model; and 3) utilizing genomic and genetic tools to identify virulence factors essential for the ecological success of Apicomplexan pathogens from both a population and evolutionary vantage. To conduct this research, our laboratory has developed a combination of new genetic, genomic, and molecular imaging techniques to identify parasite genes essential for entry into host cells, colonization, and subversion of host immunity in animal models of natural infection.

Current projects include the following:

  • Investigating Toxoplasma outbreaks associated with unusually severe clinical disease to assess the contribution of sexual meioses in the evolution of new strains that possess altered biological potential
  • Functional genomic, genetic, and bioinformatic approaches to identify and characterize discrete virulence factors that contribute to disease pathogenesis
  • Bioimaging the host-pathogen interaction in vivo using real-time molecular imaging and in situ within anatomically intact host tissues to visualize host immune cells responding to parasite infected targets
  • Gene expression, structural, and immunological analyses of parasite cell-surface antigens that regulate host immunity and contribute to parasite infectivity

Because relatively little is known about eukaryotic pathogenic processes as compared to the field of bacterial or viral pathogenesis, it is likely that entirely new mechanisms and principles of pathogenesis will emerge from our work.

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Biography

Dr. Grigg earned his B.Sc. in 1989 from the University of British Columbia. He obtained his Ph.D. and D.I.C. in 1994 from the Imperial College of Science, Technology, and Medicine, University of London. From 1994 to 1997, Dr. Grigg was a Howard Hughes Medical Institute senior fellow at the University of Washington. From 1997 to 2001, he trained as a postdoctoral scholar in molecular parasitology at Stanford University. In 2002, he was appointed as an assistant professor of medicine, microbiology, and immunology at the University of British Columbia. In 2006, he joined the Laboratory of Parasitic Disease as a tenure-track investigator.

Research Group

Alessandra Commodaro

Leanne Goodrich

Melissa Chiasson

Katie Haman

Andrea Kennard

Mourad Barhoumi

Viviana Pszenny

Sundar Natarajan

Gezahegn Gorfu Tolla

Selected Publications

Wasmuth JD, Pszenny V, Haile S, Jansen EM, Gast AT, Sher A, Boyle JP, Boulanger MJ, Parkinson J, Grigg ME. Integrated bioinformatic and targeted deletion analyses of the SRS gene superfamily identify SRS29C as a negative regulator of Toxoplasma virulence. MBio. 2012 Nov 13;3(6).

McLeod R, Boyer KM, Lee D, Mui E, Wroblewski K, Karrison T, Noble AG, Withers S, Swisher CN, Heydemann PT, Sautter M, Babiarz J, Rabiah P, Meier P, Grigg ME; Toxoplasmosis Study Group. Prematurity and severity are associated with Toxoplasma gondii alleles (NCCCTS, 1981-2009). Clin Infect Dis. 2012 Jun;54(11):1595-605.

Carlson-Bremer D, Johnson CK, Miller RH, Gulland FM, Conrad PA, Wasmuth JD, Colegrove KM, Grigg ME. Identification of two novel coccidian species shed by California sea lions (Zalophus californianus). J Parasitol. 2012 Apr;98(2):347-54.

Wendte JM, Gibson AK, Grigg ME. Population genetics of Toxoplasma gondii: new perspectives from parasite genotypes in wildlife. Vet Parasitol. 2011 Nov 24;182(1):96-111.

Wendte JM, Miller MA, Lambourn DM, Magargal SL, Jessup DA, Grigg ME. Self-mating in the definitive host potentiates clonal outbreaks of the apicomplexan parasites Sarcocystis neurona and Toxoplasma gondii. PLoS Genet. 2010 Dec 23;6(12):e1001261.

Dubey JP, Reichard MV, Torretti L, Garvon JM, Sundar N, Grigg ME. Two new species of Sarcocystis (Apicomplexa: Sarcocystidae) infecting the wolverine (Gulo gulo) from Nunavut, Canada. J Parasitol. 2010 Oct;96(5):972-6.

Visit PubMed for a complete publication listing.

Last Updated February 14, 2013