Translating information on genetic risk for body weight regulation into molecular mechanisms can have asignificant impact on intervention and therapies. We are seeking to identify genetic variation and theirmolecular mechanisms that influences obesity through direct effects on the hypothalamus as it is the brain hubthat regulates energy homeostasis and there is now considerable evidence for genetic influence to impact thisbrain region.

Replication fork stalling and collapse is a major source of genomic instability and subsequent neoplasia. Such stressed forks can be conservatively repaired and restarted using homologous recombination (HR) repair, initiated by generating an endogenous nick at the fork junction. While there are candidate nucleases for generating this DSB, most mammalian stressed forks can be restarted without these nucleases, and the origin of this nick remains undefined.

Alzheimer's disease (AD) affects 5.5 million Americans producing cognitive deficits and mortality. Thereis no treatment for AD, thus, development of interventions to slow or reverse AD symptoms is a critical area ofresearch. Furthermore, AD is difficult to detect until substantial neurodegeneration has already occurred. Thisproposal investigates proteasome function both as an intervention to AD symptoms and as a tool for earlystage diagnosis in peripheral tissues. A key symptom of AD is proteostatic dysfunction.

Postoperative complications and readmissions rates are higher in minority and low socioeconomic status (SES)patients. Low SES is associated with frailty, one of the best predictors of 30-day postoperative complicationsand early hospital readmission. Despite their influence on health outcomes, frailty and social risk factors are notconsidered in risk adjustment for reimbursement and quality measures. CMS developed financial incentive-based programs to improve quality of care.

Primary screening to take place at Calibr. Assays will be run in 1536wp format, using vital luciferase readouts at 48 and 72 hours post-infection (hpi) to detect compounds with activity throughout the P. berghei liver stage. Primary screening will be single concentration; the concentration to be screened will be determined based on library-specific recommendations, and approved by MMV.

The use modeling techniques to understand tuberculosis granulomas.