Center for Nanostructured Biomimetic Interfaces (CNBI) Contact: Mark Worden

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1 Center for Nanostructured Biomimetic Interfaces (CNBI) Contact: Mark Worden

2 Membrane Proteins Gene Expression Cell membrane (lipid bilayer) Membrane Protein functional dysfunctional Healthy rganism Diseased rganism 2

3 Michigan Life Sciences Corridor (MLSC) Gene Expression Protein functional dysfunctional Healthy rganism Diseased rganism 3

4 Core Technology Alliance (CTA) Bioinformatics Proteomics Gene Expression Genomics Structural Biology Protein functional dysfunctional Healthy rganism Diseased rganism Animal Models 4

5 Protein Expression Lab (PEL) Director: Mark Worden Manager: Dr. Jun Sun Mission: Mass produce recombinant proteins 3258 Eng. Bldg Phone:

6 Putting Membrane Proteins to Work Michigan is world-class in membrane proteins Research expertise Infrastructure Membrane Protein How to leverage this world-class stature? 6

7 Nanostructured Biomimetic Interfaces Membrane protein Expresses a desired activity Lipid membrane Anchors membrane protein Maintains active conformation Adjuvants Novel interfacial architectures Enhance protein activity Reporting mechanism Measure activity of interface Determine structure of interface Protein channel Electrode Lipid bilayer Hydrophilic layer Spacer molecules 7

8 Nanostructured Biomimetic Interfaces Allow membrane protein activities to be harnessed Leverage MI infrastructure and expertise in membrane proteins Broaden expertise to local environment around protein Provide outstanding potential for technology development Complexity of system requires a center-level approach Protein channel Electrode Lipid bilayer Hydrophilic layer Spacer molecules 8

9 Center for Nanostructured Biomimetic Interfaces Director: Mark Worden Mission: Develop new biomimeticinterface architectures that express membrane-protein activities Funding: $1.4 million MTTC grant Website: Research team (11 co-pis) Engineering (4) Nat. Sci (3) Medicine (1) Michigan Molecular Institute (2) Neogen Corp (1) 9

10 CNBI Research Team Team Member Component Contribution to Project Michael Garavito proteins cloning, expressing, and purifying membrane proteins Mark Worden proteins, reporting protein production, biosensor development Greg Zeikus lipids, proteins dehydrogenase enzymes, novel membrane lipids Rawle Hollingsworth lipids membrane lipid purification and synthesis Petar Dvornic adjuvants incorporation of dendrimers into interfaces Steve Kaganove adjuvants synthesis of dendrimers, polymer chemistry Ilsoon Lee adjuvants assembly of patterned, nanostructured interfaces Robert foli reporting total internal relection fluorescence microscopy Andrew Mason reporting integrated circuit design, fabrication of sensor arrays Donna Wang applications apply biomimetic interfaces in medical research Paul Satoh applications apply biomimetic interfaces in commercial products 10

11 CNBI bjectives Express and purify proteins having special utility Incorporate these proteins into biomimetic interfaces Apply physical, electrical, and optical methods to optimize properties of the biomimetic interfaces Develop novel biomimetic-interface technologies Nanostructured electrochemical biosensors High-density biosensor arrays High-throughput drug-screening systems Research tools to study protein activities Patent and commercialize the technologies 11

12 3-D, Nanostructured Architectures Novel biomimetic-interface assembly methods Microcontact printing Layer-by-layer self assembly 3-D, nanostructured architectures Proteins impart desired activities Protein Polyelectrolyte multilayers Dendrimers Surface 12

13 Bioelectronic Interfaces Electrical current drives reactions Proteins coupled to electrodes Electrons carried by molecular wires Applications Biosensors Biocatalytic reactors trifunctional linker H 3 C S CH C HN NH C boronate linker mediator S N B H H 3 C N N CH 3 NH 2 P P H Current (µa) cofactor N N NH 2 N H H Voltage (mv)

14 Biosensor Arrays Protein-based biosensor arrays Silicon-based integrated circuits Biomimetic interfaces added Prototype demonstrated Next-generation chips fabricated Thallium Ferricyanide Current (µa) Voltage (mv) 14

15 Research Proposals Protein Production for Biosensors, Biocatalysis, and Fuel Cells (NR) Funded for $70,000 Biomimetic Interfaces for High-Density Biosensor Arrays (MSU IRGP) Funded for $75,000 Center of Excellence in Structural Biology of Membrane Proteins (Michigan Research Excellence Fund) funded for $2,000,000 Functional and Nanostructured Biomimetic Interfaces (Michigan Technology Tri-Corridor) funded for $1,400,000 Nanomedicine Center (NIH, planning proposal submitted) Protein Structure Initiative Center proposal (NIH) NIRT: Self-Assembling Interfaces for Bioelectronic Applications (NSF) Multiphase Biocatalysis Using Biomimetic Interfaces (USDA) Dendrimer-Enhanced Cofactor Regeneration for Bioelectronic Sensors (NSF) Molecular Sensing of Sodium Homeostasis (NIH) (Green indicates funded proposal) 15

16 Potential Economic Benefits New classes of high-value products Biosensors, drug-screening systems, research tools to study protein function, etc. Highly leveraged, generic product platforms Substitute new protein to obtain new product Thousands of human membrane proteins 30-50% of drug targets are membrane proteins Protein availability is major limiting factor CTA provides Michigan a leadership position Job creation to manufacture products 16

17 Educational Benefits Experiments transferred from PEL to teaching laboratories Students trained in the PEL Graduate students Multidisciplinary Bioprocessing Lab (MBL) course students Hourly student assistants Skills being learned Molecular biology Computer-controlled fermentation Protein separation 17

18 Summary Biomimetic Interfaces research topic leverages World-class MSU expertise in membrane proteins Life-Science infrastructure investments MBI pilot-plant facilities utstanding opportunities for research funding utstanding opportunities for technology devt. Biosensors, drug screening, protein-research tools Strong connections with Michigan industry 18