The Technologies of Protein Biochips and Arrays

February 22, 2001

Scientists discuss the Technologies of Protein Biochips and Arrays.

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Bio Online: Welcome to Bio Online's live discussion on Protein Biochips and Arrays. Attempts are underway to adapt the high throughput, spatially addressable, chip and array format to proteins to create tools to study protein expression and interaction. The chemistries of DNA and protein are quite different, however, and successful platforms have to account for the complex structure and low cellular abundance of many interesting proteins. Bio Online has invited representatives from leading groups in protein chip and array development to discuss these challenges and the wide spectrum of solutions.

Stephanie O'Brien: Good morning, I'm Stephanie O'Brien and I'll be moderating today's discussion on Protein Biochips and Arrays. Now, I would like to introduce our panelists. We are very fortunate to have with us Christopher Pohl, Vice President of Research and Development, Ciphergen Biosystems, Brian Haab, Ph.D., Special Program Investigator, Van Andel Research Institute, Gavin MacBeath, Ph.D. CGR Research Fellow, Center for Genomics Research, Harvard University. I would like to begin by asking each of you to describe your research in the area of protein biochips and arrays.

Chris Pohl: My interest in Protein Biochips stems from a career-long involvement in the study of the interaction of molecules at surfaces. While this study was originally focused on the development of stationary phases targeting small molecules for commercial liquid chromatography applications, my work has expanded in scope over the past decade to include a wide variety of biological molecules ranging from amino acids to carbohydrates, nucleic acids, peptides and proteins. It is my interest in the latter that brought me to Ciphergen in order to play a lead role in the development of ProteinChip technology. While a number of commercial products are currently available from Ciphergen, my active interest focuses on development of next generation 'chromatographic' surfaces suitable for profiling and activated surfaces suitable for covalent linkage of proteins necessary for protein-protein interaction studies.

Brian Haab: I am interested in applying microarrays of proteins, peptides, antibodies, and phage display clones to the study of the molecular composition of human blood serum, particularly with the aim of identifying measurable changes that occur as a result of disease. Microarrays give the capability to efficiently and rapidly screen reagents for binding to serum proteins. Two-color comparative fluorescence is used to quantitatively compare and identify differences in the protein populations of two samples, for example disease serum and normal serum. The differences in protein abundances can be used to develop diagnostic assays or to further investigate the underlying biology. We are currently studying proteins found in the sera of prostate cancer and breast cancer patients, as well as continuing to develop protein microarray experimental methods.

Gavin MacBeath: As more and more DNA sequence information becomes available, we are left with the exciting but formidable task of deciphering protein function. My lab has approached this problem from two directions. First, we have developed microarray-based methods that enable the rapid and parallel screening of small molecule libraries to identify new ligands for selected proteins. Such compounds, which may either induce or inhibit their target proteins, can then serve as powerful tools to dissect protein function in vivo. Secondly, we have recently developed methods to array purified proteins at extremely high spatial densities on glass slides in such a way that their folded conformations are preserved. These arrays enable us to screen rapidly for protein-protein interactions, enzyme-substrate interactions, and protein-small molecule interactions. As a further application of this work, we are currently developing antibody arrays to address the difficult problem of quantifying protein abundance, modification, and localization in biological samples.

Stephanie O'Brien: Proteins are very sensitive to the physical and chemical properties of the substrates to which they are attached. Given this, what kinds of materials can be used as the solid support for the construction of protein arrays?

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