We propose a program to enhance the training and career development of scientists who seek to undertake interdisciplinary biological and biomedical research that draws upon ideas and tools from mathematics, physics, engineering and computer science, as embodied by the young field of Systems Biology. The program is centered upon a three-week intensive course at UC Irvine, followed by one to two years of follow-up mentoring and career development activity. The course is intended for graduate students, postdocs and more advanced scientists, both those with backgrounds in experimental biology—who typically need additional preparation in mathematics and computation—and those with backgrounds in mathematics, physics, engineering or computer science—who usually need additional preparation in the foundations of biology. We aim to train around 20 individuals each year. The proposed program begins with a one-week preparatory workshop, followed by a two-week core course in which lectures and laboratory modules will expose participants to cutting-edge interdisciplinary methodologies and research topics. The program will also feature extensive mentoring and career-skill building activities, including panel discussions, presentations, mentored team projects, and individually-guided development of research or fellowship proposals. These activities will involve 27 UCI faculty with research and teaching expertise in mathematics, physics, computer science, engineering and the biological sciences. Outreach activities include dissemination of information through online resources and a systems biology regional conference, as well as participation in workshops at interdisciplinary and minority conferences. The specific goals of the course include (i) conveying an understanding of Systems Biology and its interdisciplinary nature; (ii) filling gaps in technical expertise and vocabulary, and developing a deep understanding of mathematical models; (iii) acquainting participants with the challenges of collaboration and communication in interdisciplinary research, (iv) fostering community building, and (v) enhancing career development. Lecture materials (video-recorded), training datasets, and software tools will be made freely available through on-line distribution to maximize outreach. Course administration and logistics will be handled by the UC Irvine Center for Complex Biological Systems (CCBS), an NIH-designated National Center for Systems Biology.