Chemistry-Biology Interface Training Program

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1 ChemistryBiology Interface Training Program University of Massachusetts Amherst Biochemistry & Molecular Biology Chemistry Polymer cience & Engineering Chemical Engineering Veterinary & Animal ciences Molecular & Cellular Biology

2 CBI Mission Promote training and research in areas that cross the interface between Chemistry and Biology. Train chemists to speak the language of biology. Train biologists to speak the language of chemistry. CBI Alumni have gone to positions in industry & universities, including: Albany Molecular Abbott Laboratories Cubist Inc. National Institutes of tandards and Technology (NIT) Technion University University of Virginia

3 Who Are We? 24 CBI Faculty from five departments: Biochemistry & Molecular Biology Chemistry Chemical Engineering Polymer cience & Engineering Veterinary & Animal ciences 61 CBI tudent Program Members are drawn from the departmental graduate programs and the graduate program in Molecular & Cellular Biology

4 CBI Research Areas Novel Molecules for Biomedicine and Biotechnology Molecular Machines and Pathways in the Cell tructural Biology & Mechanisms of Proteins & Nucleic Acids

5 How proteins work: structure is related to function. Lila Gierasch How do chains of amino acids fold in 3D to make active proteins inside the cell? Igor Kaltashov How is the ability of transport proteins to bind and release ligands when necessary controlled by their environment?

6 How proteins are sorted and targeted by cells. Danny chnell How do proteins know where to go inside the cell? Dan Hebert How are proteins degraded when the cell finishes with them?

7 How proteins, DNA and RNA work in molecular machines. Active conformation of p53 binds DNA and enhances transcription of target genes Joe Jerry Tumor suppression by p53 Robert Zimmermann How do RNAs and proteins work together to make the ribosome protein synthesis machine? Craig Martin Transcription dissecting structure/function in a complex molecular process RNA polymerase initiates at a unique site Binding site for ribosomal protein 8 in 16rRNA

8 How proteins translocate and repair DNA. Karsten Theis How do proteins translocate along DNA and repair DNA? ATP ssdna translocating through ahemolysin channel M. Muthukumar How does DNA/RNA translocate through protein channels? Xray structure of the repair protein UvrB Cartoon of ATP hydrolysisdriven translocation along DNA

9 How cells communicate with other cells and with their environment. Dave Gross How do proteins on the surfaces of cells send signals that control cell growth? Bovine oocyte. DNA (blue), Factin (red) Richard Vachet Do phytoplankton generate ligands to acquire trace metal and/or cope with toxic metals? What are these ligands?

10 In the CBI Program we study How membrane proteins transmit information into cells. Lynmarie Thompson How are ligandinduced conformational changes propagated across the membrane to activate an enzyme?. Bob Weis Bacterial chemotaxis receptor How do ligandprotein and proteinprotein interactions integrate and amplify the signals?

11 How nature uses metals to do chemistry. Mike Maroney How are metallocenters assembled? How are metals used to catalyze biological reactions? + O 2 OH Form A H O Ni Fe CO Form B H O Ni Fe CO Decreasing Potential Ni I u I r I a H O Fe CO Ni Fe CO Form C X X Ni Fe CO Ni R Fe CO 200 K hn ICO Ni O C Fe + CO Form L CO X X Ni Fe CO Fe Mike Knapp How do metalloenzymes oxidize proteins and metabolites? Can we control this chemistry?

12 How to harness cells and molecules for medicine. Drug. Thayumanavan How can we deliver chemotherapeutic molecules specifically to tumor cells? Ligand Overexpressed receptors Tumor Cells imprint crosslink Vince Rotello Can we recognize biomacromolecules for biological and therapeutic applications? centrifuge imprinted nanoparticle usan Roberts How can we optimize the plant cell culture production process for paclitaxel synthesis?

13 How to use surface chemistry to control cells. Maria antore How can we manipulate cellular behavior via adsorbed protein conformations? Greg Tew How can we design amphiphilic surfactants to selectively disrupt bacterial membranes? Bacterial Inner Membrane Mammalian Membrane

14 In the CBI Program we use A variety of chemical tools to address biological questions. Bioorganic chemistry Bioinorganic chemistry Biophysical chemistry Bioanalytical chemistry Biochemistry We synthesize organic and inorganic model compounds that mimic enzyme active sites, that we can harness to probe or control biological systems. We use mass spectrometry, NMR, EPR, fluorescence, and calorimetry to investigate protein structures and mechanisms, to measure thermodynamics and kinetics of protein folding and catalysis. We use molecular biology, genetics, and a wide array of biochemical techniques to express and alter proteins, determine their role and binding partners in the cell, to assemble molecular machines.

15 In the CBI Program we have CBI Curriculum Chemical sciences Biological sciences CBI courses Monthly Chalk Talks Drug Design Ethics Workshop tudent Lunch eminar pecial CBI eminars CBI Retreat For more information: CBI Reading Room CBI Traineeships Lederle Graduate Research Center CBI Travel Grants

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