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The institute is headed by the director who reports through the faculty of Natural Sciences at the University of the Western Cape, and provides overall leadership to the organization.

The faculty members report to the director and are tasked primarily with provision of research, education and capacity building. Currently there are two professors and an associate professor. Several other associate faculty members are based at institutions outside SANBI but work closely with SANBI on projects through which they share funding.

Post doctoral fellows conduct research, assist with training and proposal and grant writing. Each post doctoral fellow reports to his or her faculty member. To support its capacity building activities, SANBI offers Honors modules, Masters and PhD degree certification through the University.

Human resources, administration staff and personal assistants report through assigned faculty or to the director of the institute. Several skilled IT staff support the internal IT infrastructure, as well as the bioinformatics tools and services offered by SANBI to external clients.