On May 2, 2006, the CBC selected the first set of Catalyst Award recipients. Twenty-four applications were reviewed in a two-stage process by the CBC’s 9-member Scientific Review Board. Applications were evaluated with respect to the criteria outlined in the Call for Proposals:
- inter-institutional collaboration
- focus on systems biology
- scientific merit
- appropriateness of budget
- likelihood of setting the stage for a major proposal for external support, such as an NIH Center grant.
Four collaborative groups received awards:
Martha Bohn (Northwestern), Raymond Roos, (U. Chicago), and Scott Brady (U.I.C.)
Viral Vector Translational Resource Center
$100,000 over I year
The CBC Viral Vector Translational Resource Center will promote gene therapy studies in Chicago in the field of neuroscience, by constructing the viral vectors that are necessary for introducing new DNA into diseased cells. A viral vector is basically an artificial virus and is made using genetic engineering techniques to replace virus genes with genes of scientific interest. The engineered viral vector can be used to infect the patient and instead of causing disease, the viral vector is designed to deliver new healthy genes to specific cells.
Gene therapy for human disease is gaining momentum as a direct result of information coming from the genome project. Gene delivery by viral vectors is also useful for generating novel experimental models of disease in animals and for making genetically modified stem cells. The CBC Viral Vector Resource center will produce high quality research-grade stocks of two types of viruses known to be useful for understanding gene function in the nervous system: adeno-associated virus (AAV) and lentivirus (LV). The viruses are modified so that they are merely tools for delivering experimental or therapeutic genes to cells. New virus or disease does not result from infecting cells with these viruses. The viruses will be made for approved projects on a no-strings-attached basis at a subsidized fee for service. The center will also provide advice on the use of these viruses and gene therapy study design.
A Steering Committee composed of faculty at the three institutions will take an active role in promoting the center and approving projects on a scientific merit basis. It is expected that approved projects will lead to novel gene therapies. The CBC center is an important step toward establishing the first National Viral Vector Translational Resource Center in the country to promote gene therapies for neurological disorders.
Richard Carthew (Northwestern), Sam Ming Wang (Northwestern), and Chung-I Wu, (U. Chicago)
Functions and Evolution of micro-RNAs
$200,000 over 2 years
In the last century, geneticists have successfully unraveled the molecular basis of many important traits, including some of the most devastating human diseases. Most of these are "simple traits" that are associated with severe defects in single genes. However, the majority of important and interesting traits, including most hereditary diseases and normal variations among humans, have very complex genetic bases. Hence, searching for groups of genes that can generate complex traits is a potentially rewarding avenue of research. The existence of "microRNAs," one of the most fascinating genetic discoveries of the last decade, is promising in this respect. Each microRNA controls a very large number of target genes but all microRNAs carry out the task in much the same way. It is therefore a mechanism that can generate complexity but may at the same time be fundamentally simple. Our research aims at finding out how microRNAs may vary in their production and function between closely related species, or even among members of the same species. Such variability may potentially account for some of the variation in traits, including disease propensity, among individuals.
Wen-Hsiung Li (U. Chicago) and Peter Nelson (U.I.C.)
Advanced System for Comparative Analysis of Metabolism
$135,000 over 1 year
A metabolic process involves a concerted interaction of many cellular components. Understanding the complex processes governing metabolism requires a systems biology approach and exploration of a biological system at various levels of organization: genomic, metabolic, and enzymatic. Our goal is to develop a computer system that can be used to compare metabolic processes from different organisms, so that we can identify variations in metabolic pathways and enzymes among taxonomic groups of organisms and can understand the mechanisms of adaptation to environmental changes. We also want to apply this system to biomedical research, such as how to quickly identify a bacterial pathogen, a tool that is much needed in bio-defense. To pursue this multidisciplinary subject we have formed a research team that includes biologists, evolutionists, and computer scientists, so that we can develop databases, mathematical models, computer algorithms, and computer interfaces, and can conduct systematic analyses of biological data.
Alfonso Mondragon (Northwestern) and Tao Pan (U. Chicago)
Epigenetics of RNA: a systems approach
$200,000 over 2 years
While the genome sequence encodes the master plan of how an organism works, adapts, and evolves, epigenetics deals with how this master plan is put into practice through chemical modifications of DNA, protein, and RNA. The epigenetic modifications of DNA selectively regulate gene expression. Epigenetic modifications of proteins are crucial for signal transduction and protein activity regulation.
RNA is also epigenetically modified, although this process is not as well studied or understood. Over 100 types of chemical modifications have been identified in thousands of sites in RNA from bacteria to man. However, only a few RNA modifications are essential for life. Instead, many RNA modifications are involved in stress responses and environmental adaptation. An important aspect of RNA modifications is that they may be functionally analogous to protein modifications since many of these modifications are chemically reversible. Reversible modifications would allow sophisticated regulation of the structure and function of modified RNAs.
Our work is concerned with the development of high-throughput methods to study the molecular and mechanistic details of RNA modification enzymes and to study the function of RNA modifications at the genomic level during cell growth and adaptation. Our combination of structural, biochemical and biological approaches should provide a new and unique view of the systems biology of RNA epigenetics.