Horacio Frydman

Assistant Professor of Biology
Ph.D., Johns Hopkins University, Baltimore 2002

Host-microbe interactions at the molecular, cellular and organismal level; Mechanisms of bacterial transmission through stem-cell niche infection

My research generally focuses on understanding how microorganisms and their hosts interact at different biological levels (e.g. molecular, cellular, genetic, ecological and evolutionary). Specifically, I am interested in the interactions of the intracellular bacteria Wolbachia with their host cells. The infection of invertebrates by Wolbachia represents one of the great pandemics on this planet. Even though Wolbachia is one of the most abundant intracellular bacteria on earth, infecting up to 70% of arthropods and filarial nematodes, their mechanisms of transmission are poorly understood.

Beyond fundamental questions of host-microbe interactions, understanding Wolbachia biology also has specific medical relevance.   (i) Closely related Rickettsial bacteria cause many vector-borne emerging human diseases, such as diverse forms of typhus and spotted fever .   (ii) Wolbachia provides new approaches to treat human and animal filariasis - devastating diseases including river blindness and elephantiasis - caused by parasitic worms .   (iii) Wolbachia is a potential agent to control insect vectors that transmit diseases such as dengue, filariasis and malaria.

The broad aim of my laboratory is to identify the mechanisms required for maintenance of Wolbachia infection through successive generations of their host (vertical transmission) and for infection into new hosts (horizontal or infectious transmission). My work demonstrates that Wolbachia preferentially populate the stem cell niche, the region of the fly ovary containing the stem cells. Tropism for the stem cell niche provides a previously undetected route to reach the germ line. The targeting of stem cell niche by Wolbachia may facilitate their horizontal and vertical transmission.

Our main focus is to understand the mechanisms of Wolbachia targeting of the stem cell niche and how it relates to their successful transmission. The specific questions are:

· Evolutionary conservation of niche targeting:   Is stem cell niche tropism a widespread occurrence in nature?

· Mechanism of stem cell niche tropism: Which bacterial and host factors are involved in stem cell niche tropism?

· Manipulation of host cell processes: What are the effects of niche infection in ovary stem cell activity and overall fecundity?

· Interplay between bacteria and the host signaling system: How do Wolbachia affect and are affected by the signaling pathways present in the stem cell niche?

Frydman, H.M . Wolbachia infection in Drosophila (2007) JoVE (Journal of Visualized Experiments). Issue 2: March 1st, 2007.

Beaucher M.; Goodlife, J.; Hersperger, E.; Trunova S.; Frydman, H.M .; Shearn, A. (2007) Drosophila brain tumor metastases express both neuronal and glial cell type markers. Developmental Biology 301 (1), 287- 297

Frydman, H.M .; Li, J.M.; Robson, D.; Wieschaus, E. (2006) Somatic Stem Cell Niche tropism in Wolbachia. Nature 441 (May 25 th ), 509-12.

This work is highlighted in Nature , "Authors -Making the paper" section.

Frydman, H.M. Isolation of live bacteria from adult insects (2006) Nature Protocols

Ferre * , P.M.; Frydman, H.M * ; Li, J.M.; Cao, J.; Wieschaus, E.; Sullivan, W (2005). Wolbachia Utilizes Host Microtubules and Dynein for Anterior Localization in the Drosophila Oocyte. PLoS Pathogens 1(2): 111-124   (e14)

* these authors contributed equally to this work.

This work was covered in Nature , Research Highlights v437 (27 October 2005).

Frydman, H.M. and Spradling, A.C. (2001). The receptor-like tyrosine phosphatase Lar is required for epithelial planar polarity and for axis determination within Drosophila ovarian follicles. Development 128, Number 16:3209-20.

The Lab on the News

click on the links for a pdf file.

English:

-An article (pdf 1) with Horacio's picture was published in Nature.

-Another little note (pdf 2) about our research published in Nature.

-An article published at the Howard Hughes Medical Institute Magazine (pdf 3)

-An article about the NEIDL published at Boston Now (pdf 4).

-An article about our research program at BU today (pdf 5)

Portuguese :

-An article published on the Brazilian newspaper "O Estado de São Paulo" (pdf 6)

-An interview with Horacio published on the Brazilian magazine "Shalom" (pdf 7)

-An article about the therapeutic application of stem cells published in the magazine "Época" (pdf 8)

-An interview with Horacio in the Portuguese Science online magazine "Ciência Hoje" (link)