Transmission aerobiology of m. Tuberculosis: genes and metabolic pathways that sustain MTB across an evolutionary bottleneck

Active Project Grant Awarded Last action

Award ID
P01AI159402
Recipient
Awarding agency
Obligated
$35,151,130

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 91% complete
Originally
Funding
  • $31,892,315.00 Federal
  • $3,258,815.00 Non-federal
Place of performance
New York, NY 10065, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Unless covid overtakes IT, tuberculosis is likely to keep its grip on its grim record of being the leading infectious cause of human death. Humans are the only known natural host and transmitting reservoir for the causative agent, mycobacterium tuberculosis (MTB). This means that person-to-person transmission through air is essential for MTB's survival as a species. Despite multifaceted efforts to reduce TB's transmissibility, TB's reproductive number, RO, remains among the highest of frequently-lethal infectious diseases. Aerogenic transmission is a stage in MTB's life cycle that must have been subjected to strong evolutionary pressures, yet our knowledge of MTB's transmission biology is sorely lacking. The problem has been nearly inaccessible to basic-science study for want of suitable technologies and animal models. This program project proposes to lay a basic-science foundation for potential new transmission blocking interventions by bringing a synergistic combination of investigators and disciplines together for a collaborative attack that mobilizes genome-wide screening under transmission-relevant conditions, characterizes MTB's metabolomic, lipidomic and biochemical responses to those conditions, introduces and improves animal models, and uses aerosol physics as a guide and tool. Project 1 will identify genes that MTB requires to survive the transitions between major states that the pathogen encounters EN route to, during and after aerosol transmission. Project 2 will identify conserved, essential metabolic programs in MTB that have evolved in response to transmission-related stresses, such as changes in humidity and gas composition. Project 3 builds on the recent discovery of cough-inducing lipids produced by MTB to characterize an even more potent tussive lipid as a virulence factor and to develop a model of cough-based transmission among guinea pigs. Project 4 characterizes the physical and rheological properties of respiratory fluids relevant to TB transmission and uses that information to control the mechanical generation of physiologically relevant, respirable aerosols of MTB. Core a ensures the efficient flow of information, personnel and materiel among these interconnected units, while core b develops a mouse model of simulated transmission using the aerosolization device and settings of project 4 and applies that model to confirm which genes MTB depends on to survive aerosol transmission to a new host.

Transactions

Action Federal Non-federal Date
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Amendment $3,188,803 $0
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Amendment $3,258,815 $0
Original award $3,258,815 $3,258,815
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Subawards

Subrecipient Amount Awarded
The University Of Texas Southwestern Medical Center Dr. Shiloh and his laboratory will work closely with the other members of the P01 project to test the transmission efficiency of various strains of… $1,777,406
Massachusetts Institute Of Technology SCOPE OF WORK Background and need Despite significant declines in global tuberculosis (TB) mortality rates, global incidence rates of TB remain comparatively… $2,109,199
Yale Univ Prof Cohen will coordinate a team of investigators at Yale (Postdoctoral fellow) and consultants located in the Republic of Moldova (Dr. Crudu) and at Simon… $585,962
Hackensack Meridian Ambulatory Care, Inc. Core B, the Animal Model Core, will install a controlled aerosolization device provided by Project 4 (L. Bourouiba) within a biologic safety enclosure in the… $2,428,479

Quick answers

Who received award P01AI159402?

P01AI159402 was awarded to Weill Medical College Of Cornell University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on May 13, 2021.

How much is award P01AI159402 worth?

$35,151,130 has been obligated on P01AI159402: $31,892,315 in federal funding and $3,258,815 in non-federal funding.

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