One of the strategies of the Francis Crick Institute is to collaborate creatively, taking a multi- and inter-disciplinary approach. Some recent work that has been facilitated by the Crick ICT team and the astronomy and physics groups at UCL and Durham Universities shows how this is can work in action.
Alessandro Costa is working on the architecture and dynamics of macromolecular machines at the Cancer Research UK London Research Institute and the Francis Crick Institute. His group has been piloting running large scale compute jobs on the DiRAC (Distributed Research utilising Advanced Computing) supercomputing infrastructure. The mission of the DiRAC resource is : "DiRAC is the integrated supercomputing facility for theoretical modelling and HPC-based research in particle physics, astronomy and cosmology, areas in which the UK is world-leading. HPC-based modeling remains an essential tool for the exploitation of observational and experimental facilities in astronomy and particle physics". However, a proportion of the capacity (10%) is reserved for non-physics problems in order to promote inter-disciplinary use of this capability.
In order to prove the feasibility of running his calculations on the infrastructure Alessandro's group has already used 28,000 CPU hours and expect this to reach 2.5 million CPU hours per year when they reach production scale. This would constitute 10% of the capacity at Durham, which means that LRI and the Crick are benefitting from all of the capacity there which is available for non-physics research.
This is a new departure for much of life sciences research in developing the use of the kind of supercomputing resource which had previously been the preserve of space science, high energy physics and earth sciences. Biologists are getting an advantage from the experience and expertise that are located in resources such as DiRAC to rapidly gain access to the kinds of resource that they now require for data synthesis and modelling.
The Durham DiRAC site noted the high level of technical competence of the LRI/Crick group and the ease with which their code has been able to run on the infrastructure. Similarly the biomedical scientists have been happy with the supportive and helpful relationship with Durham and DiRAC.
Alessandro describes his work as addressing cancer by "A hallmark of cancer cells is genomic instability, arising from errors in the mechanisms that maintain gene copy number and chromosome ploidy. Our research aims to understand how macromolecular machines involved in DNA replication function to preserve chromosome integrity. To address these issues, we employ a combination of single particle cryo-electron microscopy, molecular modelling and biochemistry, to generate mechanistic models that explain the basis of key nucleic acid transactions; for example, we are interested in understanding how replicative helicases collaborate with polymerases to couple DNA unwinding with DNA synthesis. By describing the architecture and dynamics of the DNA replication machinery, we seek to establish a molecular framework that explains how higher eukaryotes respond to DNA damage and how cell proliferation is regulated to avoid tumorigenesis."
