Grants

RADA ARCHITECTS LTD

Management and Business Professionals and Administrative Services-Management advisory services

City of Richmond

A1 Nails

PRODUCTION DISTRIBUTION COMPANIES INC

Electrical Systems and Lighting and Components and Accessories and Supplies

Enfield

Abbe RD Reconstruction

NYC Department of Cultural Affairs

ABC No Rio

City of Richmond

Abdu Saleh

NYC Department of Cultural Affairs

Abraham.In.Motion, Inc.

Oregon Business Development Department

Abrazo Style

National Institutes of Health

Academic Research Enhancement Award (AREA) for Undergraduate-Focused Institutions (R15 Clinical Trial Not Allowed)

National Institutes of Health

Academic Research Enhancement Award (AREA) for Undergraduate-Focused Institutions (R15 Clinical Trial Required)

National Institutes of Health

Academic Research Enhancement Award (AREA) for Undergraduate-Focused Institutions (R15 Clinical Trial Required)

National Institutes of Health

Academic-Industrial Partnerships (AIP) to Translate and Validate In Vivo Imaging Systems (R01 Clinical Trial Optional)

National Institutes of Health

Academic-Industrial Partnerships for Translation of Technologies for Diagnosis and Treatment (R01 - Clinical Trial Not Allowed)

National Institutes of Health

Academic-Industrial Partnerships for Translation of Technologies for Diagnosis and Treatment (R01 - Clinical Trial Optional)

Oregon Department of Energy

Community Renewable Energy Project

NYC Department of Cultural Affairs

Academy of American Poets

NYC Department of Cultural Affairs

Academy of Bosnia and Herzegovina, Inc.

City of Oakland

Support for ongoing instruction of the traditional arts of Hawai‘i through dance classes, music classes, and workshops in Hawaiian crafting, dance, music, and language.

Trail Blazer Camps, Inc.

Cultural After-School Adventure (CASA)

County Council of Dorchester County

Academy Street Shelter

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY The development of narrow-spectrum antibiotics against the Lyme disease-causing bacterium, Borrelia burgdorferi has the potential to significantly alter current approaches to the treatment and prevention of Lyme disease. Narrow-spectrum agents that affect only the target bacteria avoid issues of propagation of resistance in off-target bacteria, alterations in microbiome, and overgrowth of pathogenic bacteria. However, physical screening of compounds for activity against multiple bacteria such as through traditional high-throughput screens is highly inefficient due to its very low “hit” rate for activity against B. burgdorferi (<0.3%). Even when “hits” are found downstream testing for toxicity, studies of pharmacokinetics, and mechanisms of action are time- consuming and costly. Advances in machine learning can accelerate narrow-spectrum antibiotic development by more efficiently and comprehensively searching the vast potential space of small molecule candidates to identify the optimal balance of inhibitory properties, bio-availability, and toxicity. In this project, we propose to develop two modeling-based platforms to accelerate drug development efforts for Lyme disease using combinations of computational and experimental approaches. The first platform will use machine learning to design compounds with predicted activity against B. burgdorferi but not other bacteria using high throughput screening data from B. burgdorferi, E. coli and S. aureus. This framework will be biologically and chemically informed in an automated way using medical literature agents, predicted proteome binding, and machine learning models of bioavailability and toxicity. The second platform will focus on speeding identification of mechanisms of action of novel agents using a multi-omic profiling model across dimensions of morphology and transcriptional response to known agents to generate predictive models. In the process of developing these tools, our work will also produce drug response profiles for a diverse range of antibiotics against B. burgdorferi for the first time. We anticipate that when this project is completed, we will have developed new computational and experimental technologies that can dramatically accelerate the drug development pipeline for Lyme disease and from which drug development pipelines for other hard to treat pathogens may be created.

U.S. National Science Foundation

Accelerating Research through International Network-to-Network Collaborations

U.S. National Science Foundation

Accelerating Research Translation

National Institutes of Health

Accelerating Solutions to Improve Access and Quality of Empirically-Supported Practices for Youth Mental Health (R01 Clinical Trial Optional)