Structural Biology

All of genetic information in an organism is encoded in the DNA or RNA sequence of its genome. The genome projects that are now under way are producing vast amounts of data that will be essential for understanding the normal and pathologic physiology of humans and of the many plants and animals on which our lives depend. There are, however, many unsolved problems related to genome research, some of which are so novel that they are only now being defined as specific subjects for research. For example, how is gene expression regulated on the molecular level? How does chromosomal architecture influence the rate of gene expression? How is the three-dimensional structure of proteins defined by the amino acid sequences that are specified by the genome? What are the mechanisms of protein-protein recognition in complex biochemical processes? What processes regulate the assembly of protein complexes into organelles?

Structural biology provides some of the research tools that are necessary to solve those grand challenges in molecular and cellular biology. Current research is providing improved techniques by which to determine the high-resolution structures of macromolecules, and these methods are being used to study processes of molecular recognition, signal transduction, allosteric regulation, and protein folding. The resulting data are often of immediate practical value for such undertakings as rational drug design. They are also of fundamental theoretical value as thermodynamic and kinetic data become available to complement the structural information. The resulting synergy between different kinds of molecular data is providing the views that will be necessary to understand complex biologic processes. This critically important line of inquiry is now in its earliest stages, and considerable effort will be required to realize the practical benefits of such research. A person interested in a career in structural biology should obtain a PhD degree in biochemistry, biophysics, or structural and computational biology. Prerequisites include a strong background in computer science and physics, chemistry, biology, or mathematics.

Bioinformatics

Bioinformatics uses computer technology to solve informational problems in the life sciences, for example, the identification of DNA sequences in the human genome that are markedly similar to genes that have been identified and studied in experimental organisms such as yeasts. The computer databases of genome and protein sequences are now large enough to require new models for the analysis and comparison of biologic systems, and new algorithms are under development to integrate heterogeneous data into coherent programs. Informatics also plays a role in modeling the interactions between drugs and proteins or physiologic processes, in the diagnosis of disease, and in keeping track of huge databases, from the DNA sequences cited above to records of patient care.

Medicine is an information-based art and science, and the opportunities for computer applications are constantly expanding. Three-dimensional visualization of human anatomy is already an instructional tool, and the visual modeling of changes in tissue structure during disease progression offers parallel opportunities. Large pharmaceutical houses are especially interested in scientists with training in bioinformatics, given the explosion of new data from large-scale sequencing projects, like the work on the human genome, which will require new technologies for information processing to assist in the exploitation of data for product development. Young people with advanced training in statistics, information theory, artificial intelligence, and other aspects of computer science can make major contributions.



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