Jorge E Galan
Yale University, CT·Microbiology & Immunology
Some bacteria do not simply sit outside our cells and release toxins; they build a syringe-like machine, dock onto a human cell, and inject proteins that rewrite what that cell does. Salmonella is the best-studied example, and understanding its machinery matters practically: Salmonella species cause roughly 300,000 deaths worldwide each year, with more than a million U.S.
- Fields
Microbiology & Immunology
Biochemistry
Biology
- Topics
Salmonella
S. Typhimurium
type III secretion system
- Grants
- 3 known grants, through Apr 2031
What they work on
- Determine how short N-terminal secretion signals and dedicated chaperones direct client proteins to the type III secretion injectisome, the syringe-like machine Salmonella uses to inject proteins into host cells.
- Carry out structural and functional analysis of InvA, the export gate protein that forms the membrane conduit of the Salmonella pathogenicity island 1 secretion system and energizes secretion with the proton motive force.
- Define the in-situ architecture of the translocon, the pore-forming complex Salmonella inserts into the host cell membrane, and map its molecular interface with the needle-tip complex.
- Determine how an intrinsic host defense pathway restricts Salmonella replication inside cells, and how the bacterium's secreted effector proteins counteract that defense.
- Identify which Salmonella effector proteins trigger intestinal inflammation, a process critical to disease, and how they do so at the cellular level.
- Engineer attenuated S. Typhimurium to stimulate innate immunity through new mechanisms that may bypass tumor resistance to innate immune agonists in immunologically cold solid tumors.
- Test bacterial minicells, small bacteria-derived delivery particles, as a safer vehicle that retains immune-stimulating activity, and engineer Salmonella to deliver antigens that engage pre-existing CD8+ T cells.
More about the research
infections annually and an economic burden near $2.8 billion. Work here spans three levels of that problem, from the atomic structure of the injection machine, to the cell biology of how injected proteins subvert host defenses and trigger gut inflammation, to turning the bacterium itself into a cancer therapy.
Why it matters
Salmonella causes about 300,000 deaths a year worldwide and over a million U.S. infections, and the injection machinery under study is essential to the virulence of many other pathogens as well, so defining how it works and how its effector proteins disarm host cells could point to new antibacterial drugs and vaccines. Separately, engineering attenuated Salmonella and bacterial minicells could offer a treatment route for solid tumors that do not respond to existing immunotherapy.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Maria Lara-Tejero
Yale University, CT·Microbiology & Immunology
Determine the structure of the Salmonella type III secretion sorting platform, the part of the injectisome inside the bacterium, using cryo-EM and cryo-electron tomography.
Leigh Knodler
University of Vermont, VT·Microbiology & Immunology
Determine whether nine genes in the 40-kilobase type III secretion gene cluster on the Providencia alcalifaciens plasmid drive invasion of host cells, combining computational prediction, in vitro biochemistry and infection of cultured non-phagocytic cells.
Jun Liu
Yale University, CT·Microbiology & Immunology
Dissect how the spoke-ring-cage protein network of the Helicobacter pylori sheathed flagellum assembles and enables optimal motility, using cryo-electron tomography with genetic and biochemical approaches.
The school
Yale University: 73 labs on PI Pages, $1.5B a year on research, 438 research doctorates a year.
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