Boston Children’s Hospital
Note: Gift values are calculated at the prevailing US dollar rate at the date of the agreement.
In Collaboration with:
Gil Alterovitz, PhD
Biomedical Cybernetics Laboratory
Computational Health Informatics Program (CHIP), Boston Children’s Hospital
Assistant Professor, Harvard Medical School
Lixin Zhang, PhD
Chinese Academy of Sciences
The gift supported the work of Gil Alterovitz, PhD, and his team in collaboration with Dr. Lixin Zhang at the Chinese Academy of Science, to create a knowledgebase that leverages resistance and disordered protein region information from global TB strains and to further characterize predicted anti-TB compounds. As part of the initiative, the team completed the following tasks:
3. Developed an informatics knowledgebase that combines multiple TB genomes annotated disordered protein regions, drug resistance regions, protein surface location (e.g. buried, exposed residues in protein) and functional annotation. In the future, this database can be used to search for disordered protein region motifs that can help explain drug resistance.
4. Characterized one compound via dose-response curve and test intracellular activity using mycrobacterial organisms.
5. Characterized the binding of one compound against the predicted target, KatG.
The main research outcome of the project was the creation of a new knowledgebase that can be used to ascertain disordered region motifs in TB drug resistance for use in understanding mechanisms and developing new therapeutics as well as characterize new active compounds for TB. This gift has laid the foundation for The Mueller Health Foundation Drug-Resistant Tuberculosis Research Initiative, which is currently being funded by the Mueller Health Foundation through 2021.