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Biography

The immune system is the body's line of defense against disease-causing bacteria, viruses and fungi. In order to carry out its function the immune system must be able to distinguish self from non-self. If the immune system fails to detect foreign invading pathogens, the body succumbs to infection and possible death. On the other hand, if the system mounts an attack against its own tissues, autoimmunity can develop.

It has been recently appreciated that the crucial ability of the immune system to quickly detect foreign invading pathogens is a function of an evolutionarily ancient arm of the system, termed the innate system. Cells of the innate system have evolved to distinguish pathogens from self by recognizing highly conserved pathogen-associated molecular patterns (PAMPs) through a similarly-conserved array of surface-associated pattern-recognition receptors (PRRs). PRRs used by mammalian immune systems have been identified in organisms as diverse as horseshoe crabs, tomatoes, worms and fruitflies. In fact, some of the ground-breaking work in identifying the PRRs by which innate immune systems recognize invading pathogens was completed in fruitflies.

The social amoeba Dictyostelium discoideum is a unique model organism that exists for part of its lifecycle as unicellular amoebae but is induced to form a multicellular sporulating body upon starvation. The amoeboid cells phagocytose bacteria for nutrient uptake, and this process is utilized in higher organisms by innate immune cells to eliminate invading bacteria. Due to the ease with which they can be cultured and genetically manipulated, Dictyostelium amoebae have long been used to study the process of phagocytosis. It has not been appreciated, however, whether Dictyostelium detect bacteria using the same types of PRRs as do innate immune cells.

The research in our laboratory is aimed at studying Dictyostelium responses to known PAMPs found in bacteria, fungi and viruses. Our preliminary studies have revealed that Dictyostelium amoebae can indeed respond to known PAMPs, suggesting that elements of the pattern-recognition machinery used by innate immune systems in higher organisms are conserved. We are taking advantage of the manipulability of the Dictyostelium genome to identify and study particular gene products that may be involved in the Dictyostelium response to PAMPs. Characterization of such proteins in Dictyostelium may allow for identification of novel players conserved in the innate immune systems of mammals.  This project also involves structural characterization of known Dictyostelium immune-related proteins, being done in collaboration with Dr. Greg Snyder at the University of Maryland School of Medicine.

Our more recent work focuses on the use of Dictyostelium to identify novel bacterial virulence mechanisms.  Given that Dictyostelium phagocytizes bacteria in the soil, bacteria that have evolved mechanisms to evade D. discoideum predation enjoy a selective advantage. Many of these resistance mechanisms are similar to those used by bacteria to evade mammalian innate immune defense.  We are using next generation sequencing technology to characterize the genomic and transcriptomic interactions between Dictyostelium and bacteria that are resistant to Dictyostelium predation.  Investigations of bacterial mechanisms used to evade predation could lead to identification of novel bacterial virulence factors and host factors required for bacterial killing, which once identified can be used as targets for development of anti-bacterial therapies.  This work is being done in collaboration with Drs. Matthew Hemm, Mara Shainheit and Nadim Alkharouf at Towson, and with Dr. David Rasko at the University of Maryland School of Medicine.

Recent Publications:

(^{^^} denotes Towson University graduate student, ^{^} denotes Towson University undergraduate student, ^* denotes Bridges student.)

Snyder, ML. (2013) Bacterial discrimination: Dictyostelium鈥檚 discerning taste. Curr. Biol. 23:R443-6.

Pflaum K^{^^}, Gerdes K^{^^}, Yovo K^{*^}, Callahan J^{^^} and Snyder MD. (2012) Lipopolysaccharide induction of autophagy is associated with bactericidal activity in Dictyostelium discoideum. Biochem. Biophys. Res. Commun. 422:417-22.

Walk A^{^^}, Callahan J^{^^}, Srisawangvong P^{^^}, Leuschner J^{^}, Samaroo D^{^^}, Cassilly D^{^^} and Snyder MD. (2011) Lipopolysaccharide enhances bactericidal activity in Dictyostelium discoideum. Dev. Comp. Immunol., 35:850-6.

Courses Taught

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• Semester: Course Code  Title