David S. Roos, Ph.D.
304B Lynch Laboratory
433 S. University Avenue
Philadelphia, PA 19104
A.B. (Biological Sciences)
Harvard College, 1979.
Ph.D. (Cell Biology and Virology)
Rockefeller University, 1984.
Description of Research ExpertiseResearch Interests
- Molecular parasitology, host-pathogen interactions.
- Drug targets & resistance mechanisms.
- Evolution of eukaryotic cells & organellar function.
- Genome databases & database mining.
- Comparative genomics, computational biology.
- Toxoplasma gondii, Plasmodium falciparum.
Key words: Molecular parasitology, drug resistance, organellar targeting, eukaryotic evolution, pathogen genomics, database mining, computational biology, Toxoplasma, Plasmodium, malaria.
Description of Research
Studies in the Roos laboratory employ a variety of modern techniques in cell biology, molecular genetics, biochemistry, and genomics to study protozoan parasites, eukaryotic evolution, and host-pathogen interactions.
Our primary focus is on the phylum Apicomplexa, a group of protozoan parasites that typically replicate within specialized vacuoles inside the cells of infected animals. Plasmodium parasites cause malaria, afflicting hundreds of millions of people each year and killing millions of children, primarily in sub-Saharan Africa. Toxoplasma gondii is even more widespread, chronically infecting ~30% of the US population; this parasite is a leading source of congenital neurological birth defects in humans and farm animals, a prominent opportunistic infection associated with immunosuppressive treatments and diseases (including AIDS), and a waterborne pathogen of some concern from a biodefense standpoint.
By virtue of its evolutionary position, molecular genetic accessibility, and subcellular architecture, T. gondii has proved useful for studying central features of eukaryotic biology, and attributes specific to apicomplexan parasites. The availability of effectively complete genome sequences for several apicomplexan parasite species also opens up new realms to experimental analysis, both at the laboratory bench, and at the computer.
Ongoing projects focus on:
Genetic analysis of parasite biology -- exploiting the genetic accessibility of T. gondii to study such phenomena as drug resistance mechanisms, parasite differentiation, and immune effector molecules.
Drug targets and biochemical mechanisms of resistance -- focusing on nucleoside metabolic pathways, and elucidating function(s) of the apicoplast, a distinctive organelle acquired by horizontal transfer from an ancestral plant/alga.
Evolution and function of eukaryotic organelles -- including the apicomplexan plastid (see above), secretory pathway organelles, and cytoskeletal mechanisms involved in the assembly of Plasmodium and Toxoplasma cells.
Computational biology -- including the sequencing, analysis, and comparison of (pathogen) genomes, designing and mining of genome databases, and development of computational tools and algorithms for the analysis and integration of genomic-scale datasets.
- Comparative genomics of apicomplexan parasites and eukaryotic evolution.
- Mutant screens to identify pathogen genes affecting immune signalling.
- Characterization of a potential regulator of bradyzoite differentiation.
- Protein processing and organellar targeting in Toxoplasma gondii and Plasmodium falciparum.
Selected PublicationsLi, L, CJ Stoeckert & DS Roos : OrthoMCL: Identification of ortholog groups for eukaryotic genomes. Genome Res 2003.
Drozdowicz et al: Isolation and functional characterization of TgVP1, a type I vacuolar H+-translocating pyrophosphatase from T. gondii. J Biol Chem 278: 1075-85, 2003.
Li, L et al.: Gene discovery in the Apicomplexa as revealed by EST sequencing and assembly of a comparative gene database. Genome Res 13: 443-54, 2003.
Foth, BJ et al: Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum. Science 299: 705-08, 2003.
Bahl, A et al: PlasmoDB: The Plasmodium genome resource. Nucl Acids Res 31: 212-15, 2003.