SUMMARY The goal of the NIGMS T32 Predoctoral Training Program in Signaling and Cell Regulation is to prepare predoctoral trainees for productive research careers in the field of signaling and cellular regulation. The training faculty mentors consist of an outstanding, internationally recognized group of researchers in the Department of Biochemistry (BCHM) and the Department of Molecular, Cellular and Developmental Biology (MCDB) at the University of Colorado, Boulder, who study basic cell regulatory mechanisms through discovery and characterization of key components in biological pathways. The program mentors students to gain critical thinking skills and depth in understanding how to assimilate different scientific areas to solve problems in modern molecular biosciences, and teaches them how to use apply these skills when they enter the biomedical research workforce. Program elements include program-specific elective courses, an annual Symposium, Supergroup research conferences, seminars, and journal clubs, together with trainee monitoring through thesis committees and organizational meetings. These approaches expose students to broad, interdisciplinary scientific areas through cross-disciplinary mentorship and collaboration; provide them with rigorous training in experimental design, classical and modern technologies, and data analysis, with high standards for reproducibility; foster a proactive community effort to promote the recruitment and retention of underrepresented trainees; and support students’ progress and ability to work in teams in an inclusive environment through all aspects of their training. Coursework on responsible conduct of research instills students with an awareness of norms and expectations for conducting research with high ethical standards. Professional development and career training workshops expose students to diverse career trajectories and opportunities, with experiential coaching for planning and landing employment. By integrating SCR Program- specific coursework and activities with departmental graduate program requirements, and through mindful and responsive mentoring, the Program creates a thriving collaborative and interdisciplinary graduate training environment. The current proposal requests a NIH INCLUDE Down syndrome Administrative Supplement to the existing parent T32 program. As articulated in the proposal, 15 of the 36 SCR Training Program faculty are already actively engaged in Down syndrome-related research and training of graduate students and postdocs in this field. Thus, the SCR Training Program is well positioned, both scientifically and administratively, to oversee the mentorship of graduate students interested in Down syndrome-related research. This was demonstrated during our first INCLUDE Administrative Supplement of 2023-2024, when 4 trainees with interests in Down syndrome-associated cell mechanisms benefited from training in collaboration with Crnic Institute for Down syndrome research. Therefore, this proposal is perfectly aligned with the NIH INCLUDE Project Research Plan Component 1: Targeted high risk - high reward basic science studies in areas highly relevant to Down syndrome.

NARRATIVE The goal of this training grant is to prepare the next generation of scientists who will conduct high quality research and make new discoveries in biomedical sciences. The research focus of students who train in our program is to understand fundamental mechanisms in signaling and cellular regulation, an area which is key to the discovery of new therapeutic treatments for human diseases such as cancer, diabetes, inflammation, heart disease, immunological and neurological disorders, and birth defects, and forms a foundation for modern research in biology and medicine. The purpose of this INCLUDE supplement application to the existing parent T32 program is to enhance the robust environment for training graduate students in scientific areas that are relevant to alterations observed in Down syndrome and its co-occurring conditions.