Damian Ekiert

Assistant Professor,
Skirball Institute, Depts. of Microbiology and Cell Biology
 

PhD 2011 - Scripps Research Institute

LAB WEBSITE:
Ekiert Lab
KEYWORDS:
infectious disease; structure; microbiology; membranes and lipids; host-pathogen interactions

Contact Information
NYU Langone Medical Center
Skirball Institute of Biomolecular Medicine
540 First Avenue, 2nd Floor Lab 17
New York, NY 10016
Admin Contact
John Grosso
Tel: (646) 501-4509

The Ekiert lab uses structure-driven approaches to understand how pathogens establish infection and persist in the host, with the ultimate goal of applying our new insights to the development of the next generation of treatments for infectious disease.  Powerful new methods in structural biology [including X-ray crystallography and cryo electron microscopy (cryo EM)] have accelerated our ability to determine the structures of membrane proteins and large macromolecular assemblies, leading to mechanistic understanding and to new hypotheses that we can test in cell-based models of infection.  We are particularly interested in pathogens that present ongoing challenges to global public health, such as tuberculosis and malaria. In addition, we are also interested in understudied or orphan pathogens, particularly those with complex invasion machinery, unique cell biology, or an unusual infectious lifestyle.
 
Our work on mechanisms of virulence in M. tuberculosis has led us to begin exploring the inner workings of a novel lipid transport system called MCE that is essential for disease progression in mouse models of infection.  Remarkably, this system is conserved among all double-membraned bacteria, as well as some double-membraned eukaryotic organelles, underscoring its fundamental role in outer membrane function, yet its precise function is not well understood.  Our recent structural work on MCE transporters from E. coli has yielded important new insights into how these large multi-protein complexes transport lipids between membranes.  However, we still understand very little about the molecular function of MCE transporters, how they are involved in outer membrane biology, and how they impact replication and disease in pathogenic bacteria.  We are actively exploring these areas using a variety of molecular and genetic approaches.
 
Pathogens have evolved a wide-range of mechanisms to gain entry into host cells and tissues, and this is a second major area of our research.  A group of pathogenic eukaryotes called microsporidia are known to infect nearly all metazoans, including humans.  In healthy adults, infections are generally not life-threatening, but can be severe and sometimes lethal in children and immunocompromised individuals.  Microsporidia possess a remarkable, harpoon-like invasion apparatus called the polar tube, which mediates attachment and entry into host cells.  This apparatus is coiled inside the cytoplasm of infectious spores like a spring, but can be rapidly ejected in a fraction of a second to puncture or distort the plasma membrane of a target cell.  The ejected polar tube, which is only ~0.5 um in diameter but up to 100 um in length, mediates the transfer of the infectious sporoplasm from the spore into the host cell, where replication takes place.  While clearly a unique and remarkable machine, we know very little about the structure of the polar tube, how it is assembled, how the “harpoon” is launched, and how it mediates the transfer of the contents of the spore into the host cell, and we are beginning to try to unravel some of these mysteries.
Selected Publications: 
  • Ekiert DC*, Bhabha G*, Greenan G, Ovchinnikov S, Cox JS, Vale RD. Architectures of lipid transport systems for the bacterial outer membrane. BioRxiv. http://dx.doi.org/10.1101/064360 Ekiert DC, Cox JS. Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion. Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):14758-63.
  • Wang F*, Ekiert DC*, Ahmad I, Yu W, Zhang Y, Bazirgan O, Torkamani A, Raudsepp T, Mwangi W, Criscitiello MF, Wilson IA, Schultz PG, Smider VV. Reshaping antibody diversity. Cell. 2013 Jun 6;153(6):1379-93.
  • Ekiert DC*, Friesen RH*, Bhabha G, Kwaks T, Jongeneelen M, Yu W, Ophorst C, Cox F, Korse HJ, Brandenburg B, Vogels R, Brakenhoff JP, Kompier R, Koldijk MH, Cornelissen LA, Poon LL, Peiris M, Koudstaal W, Wilson IA, Goudsmit J. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science. 2011 Aug 12;333(6044):843-50.
  • Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, Goudsmit J, Wilson IA. Antibody recognition of a highly conserved influenza virus epitope. Science. 2009 Apr 10;324(5924):246-51.