# Systems Genetics of Tuberculosis

> **NIH NIH P01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $2,166,723

## Abstract

Systems Genetics of Tuberculosis: Program Abstract:
Mycobacterium tuberculosis (Mtb) infection outcomes are highly variable, creating a
great challenge in TB control; how do we identify those that are genuinely at risk and
deliver an intervention that will be effective for that individual? The biological
determinants of Mtb infection outcome have been difficult to define largely because
multiple variables are involved, which include genetic variation in host and pathogen and
non-genetic environmental factors. To overcome this complexity, we leveraged new
mammalian and bacterial genetic resources to create a model system that can be used
to study the effect of each of these variables in isolation and in combination. Host
diversity is incorporated using mice from the “Collaborative Cross” (CC), a newly
generated reference panel of inbred mice that reflects the diversity of an outbred
population. Bacterial variation is incorporated using large panels of Mtb strains that
reflect both naturally- and experimentally-generated diversity. Using this highly-tractable
system, the effect of controlled interventions can be assessed, and high-resolution
phenotyping can be applied to differentiate different TB-related disease states. Three
inter-related scientific projects will use this uniquely tractable experimental system to:
1) Define host determinants of TB susceptibility,
2) Identify bacterial determinants of host-pathogen preference.
3) Investigate the basis for TB vaccine efficacy in genetically-diverse populations
Through collaboration with two essential Scientific Cores focused on Mouse and Human
genetics and one Administrative Core, we will accomplish our ultimate scientific goals: to
characterize the mechanisms underlying tuberculosis pathogenesis, extend these
observations to human clinical cohorts, and use these insights to rationally-design more
effective vaccines.
!

## Key facts

- **NIH application ID:** 10219083
- **Project number:** 5P01AI132130-05
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** CHRISTOPHER M SASSETTI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,166,723
- **Award type:** 5
- **Project period:** 2017-08-05 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219083

## Citation

> US National Institutes of Health, RePORTER application 10219083, Systems Genetics of Tuberculosis (5P01AI132130-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10219083. Licensed CC0.

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