Identify Host Cell Death Pathway Targets for Tuberculosis Treatment

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NIAID seeks applicants whose research supports mechanistic studies on host cell death pathways and its impact on immune responses to Mycobaterium tuberculosis (Mtb) and Mtb/HIV co-infection to identify immune targets for development of host-directed therapies. Interested applicants can apply through the funding opportunity announcement (FOA): Identifying Host Cell Death Pathway Targets for Host-Directed Therapies for Treatment of Mtb and Mtb/HIV Co-Infection (R01, Clinical Trial Not Allowed).

Host-directed therapies (including vaccine adjuvants) have the potential to significantly improve treatment and prevention outcomes among people living with HIV with Mtb or who are at risk for Mtb infection. Understanding how Mtb modulates cell death pathways to promote bacterial spread and tissue inflammation while inhibiting the development of an effective immune response is crucial to identifying host pathways that could be targets with current or novel interventions.

Research Objectives

The primary scientific objective of this FOA is to understand the role cell death mechanisms (CDMs) play in response to Mtb infection, how Mtb subverts cell death pathways, and to identify cellular targets that could be exploited as potential host-directed therapies to treat Mtb and Mtb/HIV co-infections.

Cell death mechanisms include: 1) non-inflammatory mechanisms (apoptosis) that promote clearance of dying, damaged, or infected cells to maintain healthy tissue micro-environments and 2) inflammatory mechanisms (e.g., pyroptosis, necrosis, necroptosis) that release pathogens and pro-inflammatory molecules from dead cells leading to tissue damage and chronic disease.

Research Areas of Interest

NIAID strongly encourages cross-disciplinary applications that focus on mechanistic studies of host cell death mechanisms involving host-TB interaction, innate and adaptive immunity, and target identification for interventions. Use of relevant animal models and human in vitro models in applications is encouraged and may include, but are not limited to, tissue chips, organoids, spheroids, and three-dimensional models.

NIAID is also interested in research applications on the topics listed below:

  • Studies aimed at basic biological mechanisms of how Mtb modulates CDMs to promote infection, inflammation, cell necrosis, type(s) of cell death, and tissue damage.
  • Studies that characterize interactions of CDMs and other cell death-associated events (e.g., damage-associated molecular pattern release profiles) in the context of Mtb and Mtb/HIV co-infections.
  • Delineating interactions of CDMs with elements of the innate and adaptive immune systems during Mtb infection and the impact on host response effectiveness.
  • Studies that identify novel host CDMs and pathways activated during Mtb or Mtb/HIV co-infection.

Nonresponsive Research Areas of Interest

NIAID considers applications on the following research topics to be nonresponsive and will not review them.

  • Research focused on bacterial rather than host cell death mechanisms and pathways
  • Clinical trials

Submission and Contact Information

Application budgets are not limited but must reflect the actual needs of the proposed project. Additionally, the scope of the proposed project should determine the project period which should not exceed 5 years.

Applications are due on December 7, 2022, by 5 p.m. local time of the applicant organization.

Direct any inquiries to NIAID’s scientific/research contact Dr. Josh Radke at Josh.Radke@nih.gov or 301-761-6525.

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Email us at deaweb@niaid.nih.gov for help navigating NIAID’s grant and contract policies and procedures.

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