Isabelle Derre

Derre, Isabelle

Primary Appointment

Assistant Professor, Microbiology, Immunology, and Cancer Biology

Education

  • Postdoc, Host/Pathogen Interaction, Tufts University School of Medicine
  • PhD, Microbiology, Pasteur Institute

Contact Information

Jordan Hall, 7th floor, Room 7212
P.O. Box 800734
Charlottesville, VA 22908
Telephone: 434.924.2330
Fax: 434.982.1071
Email: id8m@virginia.edu
Website: https://mic.med.virginia.edu/derre/

Research Disciplines

Genetics, Infectious Diseases/Biodefense, Molecular Biology

Research Interests

Host/pathogen Interaction - Chlamydia Infection

Research Description

Chlamydia trachomatis is a gram-negative bacterial pathogen of tremendous public health concern. Ocular serovars lead to trachoma and genital serovars are the leading cause of bacterial sexually transmitted disease in developed countries. Vaccines are not available and despite the implementation of C. trachomatis screening programs, and the effectiveness of antibiotics to treat trachoma and uncomplicated sexually transmitted chlamydial infection, case rates are not declining and reinfection rates are increasing.

Chlamydia are characterized by a biphasic developmental cycle that occurs exclusively in the host cell. Once internalized, Chlamydia reside in a membrane bound compartment, named the inclusion and alternate between an infectious form (Elementary Body, EB) and a replicative form (Reticulate Body, RB). The cycle lasts two to three days depending upon the species.

If our knowledge of the cellular processes that are targeted by Chlamydia has greatly increased, we have only begun to identify the bacterial and host factors required for bacterial development.

In the past, genetic intractability of Chlamydia has made it challenging to fully dissect the role of virulence factors involved in pathogenesis, but tremendous advances have recently occurred and genetic tools (transformation, mutagenesis) are emerging. We have contributed to the field through the development of cloning vectors, the generation of Chlamydia strains expressing various fluorescent proteins, a conditional gene expression system and most recently a fluorescent reporter to monitor RB-to-EB transition.

We have also contributed to the field through the identification of host factors involved in Chlamydia infection using the RNAi methodology. One of our candidates led us to uncover that, in addition to vesicular trafficking, C. trachomatis hijacks the non-vesicular lipid transfer machinery at zone of close apposition (10-50 nm) between the ER and the inclusion membrane. These specialized platforms are referred to as ER-Inclusion membrane contact sites (MCSs).

Our overarching goal is to better understand the molecular mechanisms involved in the formation and function of ER-Inclusion MCS and elucidate their role in infection and pathogenesis. One of our approaches has been to identify and characterize the molecular components of ER-Inclusion MCS.

We have identified several molecular components of ER-Inclusion MCS. More specifically, we have uncovered a role for Inc proteins (a subset of Chlamydia specific Type III translocated effectors that are imbedded into the inclusion membrane) in the subversion of the endoplasmic reticulum. The recurrent theme is that, at ER-Inclusion MCS, distinct Inc proteins mediate the recruitment of and associate with specific host factors .

The inclusion membrane protein IncD interacts with the host ceramide transfer protein CERT, which interacts with ER-resident VAP proteins. Combined with data from the Engel Lab at UCSF, it is proposed that this complex is involved in lipid transfer to the inclusion. Recently, we have shown that through molecular mimicry of 2 eukaryotic FFAT motifs, IncV interacts with VAPs and is involved in tethering the ER with the inclusion membrane. Our lab has also shown that the ER calcium sensor protein STIM1, which is usually found at ER-PM MCS, is also enriched at the ER-inclusion MCS. We have unpublished data indicating that another Inc, that we named IncS, mediates STIM1 recruitment to ER-Inclusion MCS. The role of the IncS-STIM1 complex is under investigation.

Our research will further our understanding of the molecular mechanisms involved in the infection process and may reveal drug targets to facilitate the translational research development of tools to prevent, treat and control Chlamydia infection.

Selected Publications