Grand challenges are complex, large-scale scientific and engineering problems with broad scientific and environmental or economic impacts whose solution can be advanced by applying high-performance scientific techniques and resources. Grand challenges are often multi-institutional (collaborating researchers from universities, industry and government) and multi group.

An example of a grand challenge is the development of an AIDS vaccine and anti retrovirial drugs. Recently researchers at Edward Jenner Institute for Vaccine Research in Newbury, UK showed how bioinformatics methods could be used to help speed up the development of vaccines by studying fragments of 'foreign' proteins that have been shown to trigger a response by the immune system; the researchers then searched for common patterns in the sequences or structures of those proteins and used that information to create a theoretical model of the features that cause the fragments to trigger the immune response. It is proposed to apply similar methods to the AIDS and malaria vaccine projects in South Africa.

A second area where the computational sciences with access to HPC can have an immediate impact is in the area of climate change. The climate system forms one of the most significant vulnerabilities for South Africa, through impacts of seasonal variability, extreme events, and climate change. Investigation of the climate system is inherently computationally demanding, utilising sophisticated climate models based on the fundamental physics of the atmosphere. These models form one of the three largest demands on CPU cycles of any scientific research, and are typically developed on, and tailored for, supercomputer platforms. It is proposed to develop new regionally specific climate change scenarios for 2025; a particular project will be the resource planning in the Western Cape based on models developed from quantifying rainfall vulnerability coupled with impact of increased population growth in the region.