# Genetics & Clinical Cohorts

> **NIH NIH U19** · UNIVERSITY OF WASHINGTON · 2021 · $698,804

## Abstract

To achieve a 95% reduction of TB deaths by 2035 the WHO END-TB strategy states that critical introduction of
new tools, such as a vaccine, drugs and treatment regimes, and a point-of-care test are required. New tools to
eliminate TB are reliant on new knowledge of TB. Here we are utilizing genomic technology to interrogate
pathogen and host genomic variation in TB to advance our fundamental understanding of TB which is critically
required to drive innovation for the design of new vaccines and drugs to control the TB epidemic.
We will utilize our extensive clinical, epidemiological and genetic cohorts from Vietnam and Uganda which
have been complied over the last 2 decades, to discover genetic determinants of TB disease, progression and
outcome in humans and M.tuberculosis. We aim to 1/ identify genetic determinants of active pulmonary TB
disease in humans and M.tb, 2/ identify genetic determinants in humans and M.tb associated with bacterial
burden and poor disease outcome 3/ identify bacterial variants associated with transmission, using
evolutionary and epidemiological signatures of transmission. In aims 1 and 2 we will utilize a paired host and
pathogen genomic dataset from a large cohort of pulmonary TB patients, and analyze both host and pathogen
genomic data individually and in combination. In these aims we will investigate host and pathogen gene
variants associated with TB disease and clinical endpoints, as well as with “intermediate phenotypes” such as
host control of bacterial replication, bacterial survival in the host, and bacterial clearance. In aim 3 we will use
bacterial genome sequence to identify Mtb gene variants contributing to disease transmissibility by 1/
interrogating genomic signals of evolution and 2/ by utilizing epidemiological data of households with low and
high TB transmission. The aims of core A Genetics will deliver gene discoveries to the 3 projects for functional
analysis, while functional candidates identified in the 3 projects using in vitro and in vivo models will be
assessed within our clinical cohorts to bridge the “investigative” gap between TB disease models and human
TB disease. Through human and bacterial genomics, the outcome of core A will be the identification of key
mechanisms in the response to Mtb infection, Mtb transmissibility, TB susceptibility and disease outcome. This
research will have impact by advancing our fundamental understanding of TB which is essential to drive
innovation for the future control of the TB epidemic.

## Key facts

- **NIH application ID:** 10271170
- **Project number:** 1U19AI162583-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Sarah Jane Dunstan
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $698,804
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271170

## Citation

> US National Institutes of Health, RePORTER application 10271170, Genetics & Clinical Cohorts (1U19AI162583-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10271170. Licensed CC0.

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