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Dr. Orly Alter awarded more than $1.5 million in an R01 grant from the National Human Genome Research Institute
October 11, 2007
Dr. Orly Alter, Assistant Professor of Biomedical Engineering, has been awarded more than $1.5 million in an R01 Grant from the National Human Genome Research Institute (NHGRI). This grant will support a five-year project in her lab, titled "Tensor Computations For Modeling Large-Scale Molecular Biological Data: From Discovery of Patterns to Discovery of Principles of Nature."
In her Genomic Signal Processing Lab at UT Austin, Dr. Alter and her students use generalizations of mathematical frameworks that have proven successful in describing the physical world to model large-scale molecular biological data, such as DNA microarray data. DNA microarrays make it possible to record the complete genomic signals that guide the progression of cellular processes. Future discovery and control in biology and medicine will come from the mathematical modeling of these data. To this end, Dr. Alter built the first predictive models of DNA microarray data using matrix computations. She demonstrated the ability of her models to predict previously unknown biological principles with a prediction of a novel mechanism of regulation that correlates DNA replication initiation with cell cycle-regulated mRNA expression.
The new grant will support experimental work aimed at validating this computational prediction by collecting and analyzing genome-wide mRNA expression under conditions that are thought to decouple replication from transcription. These experiments, in collaboration with Dr. John F. X. Diffley, Director of Cancer Research UK's London Research Institute Clare Hall Laboratories, will test the ability of Dr. Alter's mathematical models to correctly predict biological principles. These experiments will also further illuminate the relation between DNA replication and RNA transcription.
This grant will also support the development of the first predictive models of large-scale molecular biological data that use tensor computations. The structure of these data is of an order higher than that of a matrix, especially when integrating and comparing data from different studies. Unfolded into a matrix much of the information in the data is lost. Dr. Alter and her students, in collaboration with Dr. Gene H. Golub, the Fletcher Jones Professor of Computer Science at Stanford University, will formulate analytically and implement algorithmically several possible tensor computations, and will apply these frameworks to integrative and comparative analyses of data from different studies of cancer, cellular proliferation and the cell cycle. This computational work will result in new insights into the interconnections among these biological programs as well as in innovations in the mathematics of tensor computations.
Dr. Alter's goal is to enable better understanding and ultimately also control of life processes on the molecular level. Her models may become the foundation of a future in which biological systems are modeled as physical systems are today. The predicted mechanism of regulation may be at the basis of a future where the cell cycle and cancer can be controlled.
Dr. Alter joined UT in 2004. In 2005 Dr. Alter was selected to give the Linear Algebra and its Application Lecture of the International Linear Algebra Society. She was an NHGRI Individual Mentored Research Scientist Development Awardee in Genomic Research and Analysis from 2000 to 2005, and a Sloan Foundation and Department of Energy Postdoctoral Fellow in Computational Molecular Biology from 1999 to 2003. Dr. Alter received her Ph.D. in Applied Physics at Stanford University in 1999. In 1998 she was an American Physical Society Outstanding Doctoral Thesis Research in Atomic, Molecular, or Optical Physics Award Finalist. Her thesis was published as a book, titled "Quantum Measurement of a Single System," by Wiley in 2001.
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