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Santosh Mishra on How to Build a Systems Biology Research Group

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A year ago, Eli Lilly took a gamble on a new approach to pharmaceutical research by forming the Lilly Systems Biology group in Singapore. BioInform recently corresponded via e-mail with Santosh Mishra, managing director of the Lilly Systems Biology group, to get an update on the group’s progress so far, and its plans for the future.

What core technologies do you plan to use at the Systems Biology group at Lilly and what role do you see bioinformatics playing within this context?

The core technologies that the Lilly Systems Biology (LSB) group will put together will be centered on DNA microarrays, both commercial as well as custom-designed chips. The experiments carried out on these platforms will be mainly drug-centric. The group will also explore the use of “next-generation” chip technology. In addition to mining the data generated from the microarrays, LSB will also manage and analyze data from proteomics, pharmacogenomics, chemoinformatics, and functional genomics experiments.

Bioinformatics will play the key role of being able to provide new computational tools and algorithms based on theories from various scientific disciplines to analyze, integrate, and mine all these data from various sources. It will also design, develop, and provide tools and mechanisms for the management of knowledge that will be either generated via these algorithms and/or through available literature.

What do you perceive as the most challenging computational issues for systems biology?

Traditional pharmaceutical research has focused on understanding modulations of single targets under different conditions. Current technologies, however, are making it possible to examine and analyze hundreds of gene expressions simultaneously, thereby providing the opportunity to understand biological pathways and points of interventions for potential therapeutics.

Managing and analyzing these large volumes of data (possibly noisy) is challenging. One has to be able to convert these data into information and then infer knowledge so as to be able to build hypotheses. For example, microarray experiments generate large volumes of data, and, coupled with the evolving algorithms that are used to analyze these data, it has made it very challenging to infer consistent knowledge and hypotheses.

There are many other challenging issues for systems biology: reverse engineering the genetic network(s); understanding the biochemical pathways; and understanding causal relationships of gene expression and protein interaction events under normal, diseased, and treatment/resolution (perturbed) conditions in various tissues and/or organs. Lilly Systems Biology will develop novel algorithms and models to infer these pathways and their relationships to each other and also their relationships under the influence of drugs.

Building a research center from scratch is a dream come true for many people in the field. What advantages would you say this opportunity offers you from a bioinformatics perspective? What drawbacks does it present?

The advantage this opportunity provides is to build a computational environment that can accommodate scientists’ views and be able to provide them with a platform that mimics the way pharmaceutical and biological research, experiments and subsequent analysis are carried out. This also provides the opportunity to build an integrated system for pharmaceutical research and discovery.

One disadvantage may be the time that it takes to build from the ground up. However, building such a system with hypothesis-driven features will enable Lilly’s scientists to accelerate the drug discovery and development process. Mechanisms will also be built to handle existing legacy data.

Have you settled upon any particular bioinformatics tools or technologies yet?

Most, if not all, of the standard bioinformatics tools and technologies will be incorporated into the design of the system. Standard sequence analysis tools, expression data management and analysis tools, protein and gene networks and pathways inference and analysis tools, and tools to “mine” knowledge from existing literature, etc., will all be included. Some public domain and third-party tools and data content will be evaluated, and licensed as appropriate. Heavy emphasis will be placed on developing and integrating new tools in-house that will then be integrated within Lilly Systems Biology.

Do you plan on drawing from or contributing to any of the public efforts in systems biology?

It is our intent to be able to draw on public domain efforts such as BioSpice and the Caltech/ERATO Systems Biology Workbench. Developments that do not compromise the intellectual property rights of Eli Lilly and Company will be considered for contributions to the public domain efforts on a case-by-case basis.

Have you purchased any hardware for the center yet? What factors influence your decision-making on the hardware side?

Some hardware has already been purchased for the center. The hardware includes high-speed computer servers from Sun, a Linux cluster, and terabytes of storage space from EMC.

Speed, stability, reliability, expandability, and maintainability influenced our decisions. We are also exploring the use of the grid computing technology. As the need arises, the center is prepared to explore and deploy other state-of-the-art hardware.

What data sources do you intend to draw from?

Much of our data will be generated in-house. However, depending on our needs, we intend to draw on data from all public sources, and some third-party sources.

Singapore has been making quite a push into bioinformatics recently. What advantages does the Singapore location offer you in setting up the Systems Biology group?

Lilly is a global company with a strong intent to expand our research efforts. Locating the LSB in Singapore provides access to talented scientists from the Asia-Pacific region. Close proximity to China, India, Australia, and other countries will enable highly talented scientists to relocate to Singapore more easily and allow Lilly to benefit from their cultural diversity.

The Singapore Economic Development Board (EDB) is the lead government agency promoting industrial activities in the biomedical sciences. Through its Biomedical Sciences group, the EDB promotes and enhances the range of biomedical sciences activities and ensures that there is a sound infrastructure to support such activities in Singapore. Singapore is already home to six of the top fifteen pharmaceutical companies of the world, and has a growing base of medical devices, biotechnology, and healthcare services companies. The strong support from the Singapore government will provide opportunities for synergies and collaborations among different organizations.

The government of Singapore provides strong support for intellectual property rights protections and this an important advantage to the LSB as it envisions designing, developing, and implementing novel ways of identifying drug targets and accelerating the drug discovery process.

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