The Maximizing Investigators' Research Award (MIRA) provides support for the program of research in an investigator's laboratory that is within the mission of NIGMS. The goal of MIRA is to increase the efficiency and efficacy of NIGMS funding. It is anticipated that this program will: Increase the stability of funding for NIGMS-supported investigators, which could enhance their ability to take on ambitious scientific projects and approach problems more creatively; Increase flexibility for investigators to follow important new research directions within the NIGMS mission as opportunities arise, rather than being bound to specific aims proposed in advance of the studies; More widely distribute funding among the nation's highly talented and promising investigators to increase overall scientific productivity and the chances for important breakthroughs; Reduce the time spent by researchers writing and reviewing grant applications, allowing them to spend more time conducting research; Enable investigators to devote more time and energy to mentoring trainees in a more stable research environment. This FOA allows applications from eligible NIGMS-funded investigators and from New Investigators proposing research within the scientific mission of NIGMS. The FOA also allows renewal applications from all current MIRA grantees (established investigators and those previously funded as early-stage investigators). PD/PIs who are currently Early Stage Investigators (ESIs) should apply through the ESI MIRA FOA and should not apply through this FOA.