2. Combining Arrays and Mass Spectrometry for High Throughput Discovery in Chemistry and Biology
报 告 人：1. Prof. Chad A. Mirkin（Department of Chemistry and International Institute for Nanotechnology）
2. Prof. Milan Mrksich（Northwestern University）
报告时间：2016年11月29日（星期二） 上午9：30
报告地点：张江园区办公楼大报告厅
Prof. Chad A. Mirkin
Chad Mirkin is the Director of the International Institute for Nanotechnology and the Rathmann Professor of Chemistry, Chemical and Biological Engineering, Biomedical Engineering, Materials Science and Engineering, and Medicine at Northwestern University. He is known for his discovery and development of spherical nucleic acids (SNAs) and many contributions to nanobiomedicine, nanolithography, supramolecular chemistry, and nanoparticle synthesis. He has authored over 660 manuscripts and over 1,000 patent applications (289 issued), and he is the founder of multiple companies. Mirkin has received over 100 national and international awards, and at present, he is an Associate Editor of Journal of the American Chemical Society.
Natureencodes nucleic acidsto assembleenormously complex and highlyfunctional materials that form the foundation of life.To establish a similar code to constructsynthetic, unnatural materialswould allow researchers to perfectly position the atoms in a material to perform a specific function.While such control is exceedingly difficult for atomic and molecular building blocks, it is possible to control the interactions between nanoscale componentsthrough the ligands attached to their surface,independent of nanoparticle structure and composition. Our group has shown that nucleic acids can be used as ligands to program the spacing and symmetry of nanoparticlebuilding blocks into structurally sophisticated materials.These nucleic acids function as programmable “bonds” between nanoparticle “atoms”and can be analogized to a nanoscale genetic code to direct assembly.Thetunability of these nucleic acids bonds, in terms of length and sequence, hasallowed us todefinea powerful set of design rulesto buildsuperlattices with more than 30 unique lattice symmetries, over one order of magnitude in interparticle spacing, and multiple well-defined crystal habits.These materials can dynamically respond to biomolecular stimuli, including other nucleic acids and enzymes, to tailor structure and properties on demand, analogous to how these molecules function in nature.This unique genetic approach to materials design yields nanoparticle architectures that can beusedto catalyze chemical reactions, manipulate light-matter interactions, investigate energy transfer between nanostructures, and improve our fundamental understanding of crystallization processes.
Prof. Milan Mrksich
Milan Mrksich is the Henry Wade Rogers Professor at Northwestern University, with appointments in the Departments of Biomedical Engineering, Chemistry, and Cell and Molecular Biology. He also serves as the Founding Director of the Center for Synthetic Biology and as an Associate Director of the Robert H. Lurie Comprehensive Cancer Center.He earned a BS degree in Chemistry from the University of Illinois and a PhD in Chemistryfrom Caltech. He then served as an American Cancer Society Postdoctoral Fellow at Harvard University before joining the faculty at the University of Chicago in 1996. He began his current position at Northwestern in 2011. His many honors include the Camille Dreyfus Teacher-Scholar Award, the TR100 Innovator Award, Arthur C. Cope Scholar Award, election to the American Institute for Medical and Biological Engineering and the Illinois Bio ICON Innovator Awardee. Professor Mrksich is a leader in the science and engineering of materials that contact biological environments. His laboratory has pioneered several technologies, including strategies to integrate living cells with microelectronic devices, methods to enable high throughput assays for drug discovery, and approaches to making synthetic proteins for applications as therapeutics. Most notably, he developed the SAMDI biochip technology that allows enzymes to be tested at a rate of a hundred thousand per day, and that has become the leading ‘label-free’ technology in drug discovery. His work has been described in approximately 200publications and 500 invited talks. Professor Mrksich is an active advisor in government and industry. His present and past appointments include the Chair of the Defense Sciences Research Council—an advisory group to the Defense Department—a member of the Board of Governors for Argonne National Laboratory, and Chair of the Searle Scholars Advisory Board. He has also been active as an entrepreneur. He is a Founder of 480 Biomedical, a company that has developed stents for the treatment of vessels in the leg and that are now in clinical trials. He is also Founder and Director of SAMDI Tech, a contract research organization that has commercialized his high throughput assays for discovering drug leads and that now serves global pharmaceutical companies. He has also served on a dozen Scientific Advisory Boards of other life sciences startup companies.
This talk will describe an approach for using mass spectrometry to analyze molecular arrays. The arrays are prepared by immobilizing small molecules, proteins, peptides and carbohydrates to self-assembled monolayers of alkanethiolates on gold. This arrays are then treated with reactants—either chemical reagents or enzymes—and then analyzed using the SAMDI technique to identify the masses of substituted alkanethiolates in the monolayer and therefore a broad range of reactivities and post-translational modifications—including kinase, protease, methyltransferase and carbohydrate-directed modifications—and for discovering chemical reactions. This talk will describe applications to high throughput experiments, including the discovery of reactions, the use of carbohydrate arrays to discover novel enzymes, the preparation of peptide arrays to profile the enzyme activities in cell lysates and high-throughput screening to discover novel reactions and small molecular modulators. These examples illustrate the broad capability of the SAMDI method to profile and discover molecular activities in the molecular sciences.
