1978 — 1979 |
Tirrell, Matthew Stephanopoulos, George [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Acquisition of a Real-Time Process Control Computer Facility @ University of Minnesota-Twin Cities |
0.915 |
1978 — 1980 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Research Initiation - Experimental and Theoretical Studies of Batch Copolymerization Reactor Control @ University of Minnesota-Twin Cities |
0.915 |
1979 — 1981 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nonhomogeneous Flow of Macromolecular Solutions and Melts @ University of Minnesota-Twin Cities |
0.915 |
1980 — 1982 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Copolymerization Reaction Engineering At High Conversion: Effects of Imposed and Natural Temporal Variations in Reaction Conditions @ University of Minnesota-Twin Cities |
0.915 |
1981 — 1986 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Macromolecules in Narrow Channels (Materials Research) @ University of Minnesota-Twin Cities |
0.915 |
1983 — 1985 |
Tirrell, Matthew Oriani, Richard Scriven, L. Evans, D. Fennell Davis, H. Ted |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Research Equipment: Measurement of Forces Between Surfaces @ University of Minnesota-Twin Cities |
0.915 |
1984 — 1990 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Presidential Young Investigator Award: Transport Propertiesof Macromolecules and Polymer Dynamics @ University of Minnesota-Twin Cities |
0.915 |
1985 — 1989 |
Tirrell, Matthew Ranz, William Macosko, Chris Thomas, Edwin (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Industry/University Cooperative Research: Polyurethane and Polyurea Reaction Injection Molding @ University of Minnesota-Twin Cities
Reaction injection molding (RIM) is a rapid process for producing large light weight plastic parts that are used for automobile and airplane parts among others. Low viscosity liquid reactants (monomers) are mixed and injected into a mold where they reach and form a solid crosslinked polymer product. The two feed streams impinge on each other at high velocity and thus achieve good mixing. Reaction proceeds as bulk copolymerization resulting in segmented block copolyers. The proposed research is aimed at elucidating the fundamental chemistry and physics involved in RIM. The PIs plan to carry out their work in six stages: (1) Model the mold filling and curing steps; (2) Study the chemistry of polyureas and polyurethanes; (3) Look at the role of phase separation during polymerization in the mold; (4) Study the effects of mixing in the mold (5) Obtain morphology measurements; and (6) Study the bubble motion and growth process in RIM due to injected nitrogen gas. The overall goal is to build a model for the RIM process. During the molding cycle the copolymers must grow into long chains and segregate nto hard and soft phases. The work in this project is the analysis of the combination of polymerization kinetics and phase separation dynamics within a flowing mixing, reacting and heat transferring system. The PIs are all very highly thought of and their laboratory is one of the best in the country for this work. The cooperation with industry provides an excellent input to help keep the project aimed in the proper direction. A three year Industry University Cooperative Research Grant is recommended at $154,682 for FY 86, $174,038 for FY 87, and $164,000 for FY 88.
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0.915 |
1991 — 1993 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
U.S.-Japan Cooperative Research: Block Polymers Confined Ontwo-Dimensional Surfaces: Morphology, Thermodynamics, and Application For Surface Modification @ University of Minnesota-Twin Cities
This award provides support for a cooperative research project between Professor Matthew Tirrell, Department of Chemical Engineering and Materials Science, University of Minnesota and Professor Tadao Kotaka, Department of Macro- molecular Science, Osaka University, Japan. The objectives of the project are to investigate, both experimentally and theoretically, the morphology and some aspects of the properties of model block polymers adsorbed and confined on surfaces of substrates of various types. Block polymers confined in two-dimensional regions, such as those adsorbed on surfaces of given substrates, are in a special thermodynamic state different from that of a more familiar three-dimensional bulk. Physico-chemical properties of such thin layers are very important scientifically, in the sense that surfaces may alter thermodynamic order-disorder transitions, as well as for practical applications such as adhesion, surface modification and functionalization. The researchers will study the relationships among surface morphology, molecular structure and surface physico-chemical properties of block polymers confined on two-dimensional structures, to clarify the factors controlling the surface morphology of the block polymers, and to obtain information on how to attain well- controlled surface morphology formation, modification and functionalization. The strengths of the two research teams are very complementary, the Japanese team having a great deal of experience in synthesis and characterization under conventional means and the US team having almost unique expertise in characterization of surfaces and materials in confined dimensions. These studies will hopefully yield new ways of preparing films with specific morphologies and consequently, novel properties, thus enhancing our ability to fabricate films with desired characteristics for technological applications.
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0.915 |
1991 — 1996 |
Tirrell, Matthew Russel, William Mays, Jimmy (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Tailored Interfaces With Amphiphilic Polymers @ University of Minnesota-Twin Cities
This proposal is for a three-way collaboration between U. Minnesota, Princeton, and U. of Alabama, with different but mutually enhancing expertise in synthetic chemistry and materials science, to obtain needed information on the interfacial physical chemistry of amphophilic polymer dispersants. The specific approach is to study the direct effects of systematic variations os molecular weight, chemical structure, polymer architecture, and other factors which might possibly be used for tailoring amphophilic polymer dispersants, on the interactions that determine the macroscopic properties of colloidal dispersions. Effects of systematic variation of molecular characteristics of adsorbed layers of amphophilic block copolymers on the interaction forces between two such macroscopic layers will be studied. Polymers molecules with well-defined molecular weights and architectures will be synthesized by anionic polymerization and characterized with respect to block molecular weights, compositions, and architectures. Direct measurement of forces between adsorbed layers will be made. Theoretic modelling of the measured interaction profiles using self-consistent field theory will be carried out. With the measured and qualitatively modelled interactions having been determined, the response of macroscopic dispersion properties can be related in a direct way to molecular characteristics of the dispersion agents.
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0.915 |
1992 — 1993 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
U.S.-France Workshop On High Performance Polymers, Annecy, France, June 1-5, 1992 @ University of Minnesota-Twin Cities
This award will support a U.S.-France Workshop in high performance polymers organized jointly by Matthew Tirrell of the University of Minnesota, Alain Michel of the Laboratory of Organic Materials, and Alain Fradel of Pierre and Marie Curie University, Paris, France. New developments in high performance polymer materials are of technological importance in microelectronics, ceramics, medicine and separation processes. The workshop will focus on the development of high performance properties beyond the current norm. They will address developing multicomponent materials of increased strength, chemical or thermal resistance, enhanced electrical conductivity, improved nonlinear optical properties, and effectiveness as interfacial agents. Multicomponent refers to existing composites, copolymers, blends, grafts and semicrystalline materials. The workshop participants will exchange information and review the state of the art in this area. This workshop will bring together strong French expertise and tradition in macromolecular chemistry and American experience spanning the range of chemical synthesis to processing. It is expected that future research areas, including joint activities, will be defined.
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0.915 |
1994 — 2001 |
Furcht, Leo Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Characterization of Cell Behavior in Biological Matrices @ University of Minnesota-Twin Cities
9413241 Tirrell This award to a group of 15 neurobiologist, cell biologists and biomedical engineers will support a training program focused on an important and as yet poorly understood area of biology, the interaction of cells with collagen and other matrices on which they grow. The research and training program will emphasize four aspects of this focus: one addresses the fundamentals of these interactions in both natural and artificial matrices, and the otheps address interactions occurring in connective, neural and vascular tissue. The award will support training of undergraduate, graduate and postdoctoral students through a mix of new and existing courses, rotations and optional internships that is sufficiently flexible to accommodate the needs of students that enter with backgrounds in either engineering or biology. The trainees who emerge from the program are expected to contribute to fundamental biology and to more applied areas such as tissue engineering and the development of biomimetic composite materials. This award is also being supported by the Bioengineering Program within the Division of Bioengineering and Environmental Systems and by the Human Resource Development Program within the Division of Engineering Education and Centers. ***
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0.915 |
1998 — 2000 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Workshop On Materials Design and Processing At the Nano- Andmesoscales Through Self-Assembly (January 13-14, 1998) @ University of Minnesota-Twin Cities
ABSTRACT CTS-9806973 Matthew Tirrell/U. Minn. This proposal is a Workshop on, "Materials Design and Processing at the nano- and Mesocales Through Self-Assembly' held at the national Science Foundation, January 13 and 14, 1998. The overall aim of the workshop is to discuss opportunities, means and barriers to bringing self-assembly processing of materials from their current state of laboratory innovation into the real technology and manufacturing realm. A group of more than 35 expert scientists and engineers, including 6 from industry and 4 from national laboratories, have agreed to participate in this Workshop. Th format will be a series of four plenary lectures followed by intense discussion in four topical groups. * Designing Nanostructured materials Through Molecular and Subunit Architecture * Characterization Methods and Process Control for Self-Assembly of Nanostructured Materials * Product Possibilities from Self-Assembly * Processing Routes to Self-Assembly, Nanostructured Materials The report of this workshop will be a working document for the National Science Foundation staff to provide guidance for future funding intiatives in this area.
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0.915 |
2000 — 2005 |
Yang, Tao (co-PI) [⬀] Petzold, Linda [⬀] Mezic, Igor (co-PI) [⬀] Macdonald, Noel (co-PI) [⬀] Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Itr: Computational Infrastructure For Microfluidic Systems With Applications to Biotechnology @ University of California-Santa Barbara
The applications of microfluidic devices (which involve liquids moving in spaces measured in micrometers, i.e. millionths of a meter) are growing explosively. As a specific example, consider the development of microsystems for blood testing and screening. For consumers, one could envision devices available in drugstores that could perform genetic screening for conditions of concern to individuals. At a larger scale, use of such devices in blood banks could significantly reduce the time and blood lost in screening the 14 million pints of blood donated per year. Sample preparation is a critical bottleneck in the development of integrated miniature analytical systems, and it remains largely unaddressed. It is currently done outside the microsystem by mixing, shaking, and pipetting, because there are no effective integrated design method. Improved computational methods promise to allow integration and interconnection of microfluidics. This will have an effect analogous to automated methods for VLSI design on microelectronics; it will revolutionize the field.
This project will develop a computational infrastructure for simulation and design of microfluidic systems involving non-Newtonian, micrometer/nanometer-scale flows dominated by surface-related phenomena. Computational tools and analytical tools will be developed and used to compare with theoretical and experimental results. The project emphasizes methods to deliver complex molecules to flow surfaces, to create surface reaction sites and to provide the components for molecular-scale mixing and dispensing. It will design, fabricate, and characterize both stationary and oscillating MEMS fluidic channels and surfaces to evaluate molecular-scale mixing, flow, delivery, and dispensing of complex biological fluids. The focus will be on surface dominated flow and reaction phenomena that can be scaled for delivery of single molecules to programmed reaction sites. Such surface-related phenomena should find broad application in making MEMS-based, "chip-scale" analytical instruments and "biochips". The computational tools required to analyze and design such devices are currently nonexistent. This project brings together a team of computer scientists, numerical analysts, fluid dynamicists, experimentalists, and microscale process theoreticians who will collaborate closely on creating those tools and using them.
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0.915 |
2001 — 2006 |
Deming, Timothy Safinya, Cyrus (co-PI) [⬀] Butler, Alison (co-PI) [⬀] Tirrell, Matthew Zasadzinski, Joseph (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nirt: Creating Functional Nano-Environments by Controlled Self-Assembly @ University of California-Santa Barbara
Abstract CTS-0103516 M.Tirrell, University of California-Santa Barbara
The work proposed here aims to develop the science of spontaneously dividing three-dimensional space into compartments, that is, into controlled environments, at the nanometer size scale, in order to accomplish several engineering objectives. The objectives include: controlled release of therapeutic agents (e.g., drugs, genetic materials); controlled access to biofunctional components (switching or masking activities when desirable); embedding biological signaling within 3D matrices (nano-phase-separated block co-polypeptides decorated with targeting or "homing" ligands) and using surface patterning and templating to produce novel or tailored structures and environments. Four project areas encompass and organize our overall plan: 1. Creating nano-environments via lipid encapsulation; 2. Nano-environments from peptide amphiphiles; 3. Amphiphilic block copolypeptides with hierarchical structures; 4. Patterned surfaces for self-assembly. The work we will do is conceptually similar to creating artificial cells in the sense of separating regions for different functions (without any attempt to build in self-replication). We are aiming toward bio-mimetic structures for functions that may not be naturally occurring, and that mimic or supply interesting functionality. The kinds of functions we wish to incorporate vary from biological (e.g., cell adhesion) to non-biological (e.g., fluid connectivity).
The science we will pursue is the principle of spontaneously creating compartments or confined regions with a definite inside and outside. As a practical matter, this means delving deeper into controlled formation of micelles, vesicles, domains, tubules and other controlled regions, as part of larger assemblies of nanoscale components. We will synthesize new lipid-like and macromolecular architectures to drive self-assembly in ways that can encapsulate some species and exclude or display others, controllably, on the interiors and exteriors, respectively, of defined regions. Our research will produce new materials for biomedical applications, new therapeutic approaches based on controllable binding and transport processes and new ways of integrating biological structures with semiconductor fabricated devices. Our core expertise includes extensive experience with lipid and macromolecular structure and phase behavior, based on substantial ability to synthesize new molecules. We have experience with assessing and influencing biological activities and functions, ranging from cell adhesion, to drug delivery and gene transfection, to the roles of metal ions in growth processes and pathological conditions. Characterization expertise and facilities for all of this work are readily available among the members of this collaboration: electron microscopy (adapted in several ways for soft, wet, biological samples), scanning probe nicroscopies, optical microscopy (with fluorescence, confocal, interference and video capabilities), surface force measurements, x-ray and neutron scattering, neutron reflectometry and organic synthesis.
The interdisciplinary talents of this team are essential to educate students broadly in the new fields of nanotechnology and biotechnology. The five graduate students and one postdoctoral fellow supported by this proposed grant will work in broad areas of the overall project where interests of several groups overlap strongly. In this way, the students will have continued exposure to the full interdisciplinary group of biochemists, chemists, physicists, chemical engineers and materials scientists that make up our team. An active effort is planned to attract a diverse population of students to this project. We believe that the students and fellow trained in the course of this research will be extraordinarily flexible in their talents, and therefore exceptionally, well-prepared for careers in industry or universities, because of the multiple advisor, multiple technique environment we will provide. The PI and co-PI's will manage this project to continuously promote this interdisciplinary approach in the selection of specific projects to be pursued. The efforts from this project will feed new ideas, examples and practical experience into a new laboratory-based course under development entitled, "Biomaterials Preparation and Characterization".
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0.915 |
2003 — 2008 |
Hansma, Helen Gwinn, Elisabeth (co-PI) [⬀] Chworos, Arkadiusz [⬀] Lipman, Everett (co-PI) [⬀] Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
New Applications For Probe Microscopy of Biomolecular Materials @ University of California-Santa Barbara
The main objective of this research is to develop innovations in probe microscopy of biomolecular materials. The research will integrate both the imaging and the pulling aspects of probe microscopy to develop models of biomolecular mechanics and structures. Specifically, the work will focus on three significant classes of biomolecular materials, and it will examine two types of biomaterials from each class: (1) Highly elastic biological proteins - spider capture silk and HMW (high molecular weight) glutenin -are good model systems for possible improvements in the elasticity of synthetic materials. (2) Protein mimics to be investigated are polyamino acids and a non-peptide triblock copolymer mimic of the abalone protein lustrin; lustrin is the main protein component of abalone shell, which is 3000 times more fracture resistant than concrete. (3) Novel DNA structures to be investigated are telomeric mimics, and DNA-surfactant liquid-crystalline films, which have been used to study photoconductivity of DNA.
This research will take a multi-directional approach to make innovations in probe microscopy of biomolecular materials. Probing many systems has been a good approach for maximizing the probability of innovation in probe microscopy of biomolecular materials. Undergraduate students will be involved in the research, and some will become co-authors or first authors of peer-reviewed publications.
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0.915 |
2004 — 2005 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Workshop On Self-Assembly and Self-Organization; Santa-Barbara, Ca @ University of California-Santa Barbara
The University of California, Santa Barbara (UCSB) proposes to organize and host an international workshop entitled in "Directed Self-Assembly and Self-Organization" on the UCSB campus January 12-14, 2004. Our organizational sponsoring partner on the Japanese side is The Ministry of Education, Culture, Sports, Science and Technology (MEXT). The workshop co-chairs will be Professor Masatsugu Shimomura of Hokkaido University and Professor Matthew Tirrell of the University of California, Santa Barbara. This meeting is the second in a workshop series on nanotechnology; the first, on in "Tools and Metrology for Nanotechnology", was held at Cornell University January 23-24, 2003.
A set of key questions for debate and discussion for this workshop is given in the body of the proposal. The overall objective is to bring a sharp focus on the scientific and technological possibilities for self-assembly as a route to realizable nanotechnologies. Self-assembly has thus far produced many interesting structures in the laboratory and considerable promise for manufacturing useful nanostructured products. However, this promise will remain unfilled unless we learn to diversify, accelerate, control and scale-up self-assembly processes.
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0.915 |
2005 |
Pincus, Philip (co-PI) [⬀] Kuhl, Tonya Israelachvili, Jacob (co-PI) [⬀] Alcantar, Norma [⬀] Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
U.S.-Mexico Workshop: Bridging Nanoscale Forces and Interfacial Phenomena to the Macroscopic World; Mexico; Cancun, Mexico, January 2006 @ University of California-Santa Barbara
This award will help to support a workshop on nanoscale forces and interfacial phenomena to be held in Cancun, Mexico around January 2006. Organized by Dr. Norma Alcantar of the U. of South Florida and Dr. Phillip A Pincus of the U. of California-Santa Barbara, together with international partners Dr. Tomas Viveros of the Universidad Autonoma Metropolitana in Iztapalapa, Mexico, Dr. Suzanne Giasson, of the University of Montreal, and Dr. Roger Horn of the University of South Australia, the workshop will involve representatives from approximately 42 universities worldwide and international student participation.
The meeting will bring together scientists that are international leaders in measuring and analyzing surface forces and interfacial phenomena to provide a substantive training experience for students, postdoctoral researchers and investigators who are at early stages in their career. It will feature a discussion of critical issues facing colloid and interface science. Students and postdoctoral researchers will present their work in poster sessions. Ultimately, the workshop aims to foster collaborations at multiple levels (interdisciplinary and internationally) to attack complex problems that connect the nanoscale world to the macroscopic world. The Office of International Science and Engineering and the Directorates of Engineering and Mathematical and Physical Sciences are sharing in the funding of this activity.
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0.915 |
2007 — 2010 |
Pincus, Philip (co-PI) [⬀] Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Materials World Network: Polyelectrolyte Brushes: Understanding Multi-Valent Effects On Structure and Properties @ University of California-Santa Barbara
This comprehensive program between the University of California at Santa Barbara and the Universitt Bayreuth in Germany aims at deepening understanding and uncovering new phenomena in systems of polyelectrolyte brushes immersed in multi-valent ionic media containing metal ions, charged surfactants, molecular ions, proteins and oppositely charged polyelectrolytes. Recent preliminary work via surface force measurement has shown new behavior, relative to that in mono-valent salt, of polyelectrolyte brushes in multi-valent media. The Surface Forces Apparatus has been used to demonstrate the extended configurations and long-range forces exerted by and between brushes immersed in good solvents. In particular, there are strong collapse transitions in some multi-valent media, observable of both flat and highly curved surfaces. New behavior signals new properties in a range of important applications of polyelectrolyte brushes. Polyelectrolyte surface properties in multi-valent ionic media, such as in physiological environments, surfaces of medical devices, rheology of water-based suspensions, flocculation or condensation of polyelectrolytes, or in the hard household water and surfactant mixtures in which many personal care products are employed, may not be straightforwardly inferred from experiments in mono-valent salt, which constitute our current knowledge base. Soft interfaces that consist of charged macromolecules, highly swollen with water, are the norm in biology, such as the cellular glycocalyx, the surfaces of lung tissue, eyelids and articular cartilage, and the interfaces between mineralized collagen fibrils in bone. Commercial products, such as those for personal care (e.g., shampoo, skin care), medical prostheses (e.g., joint replacements), materials processing (e.g., sterically stabilized dispersions of suspended particles or assemblies), anti-fogging surfaces, and gene chips, also often rely on highly hydrated, charged polymer interfaces.
The results of this work are anticipated to have applications in biology and medicine, water purification, water-based pigments, paints and coatings and the cosmetic product industry. By virtue of the collaboration between UC Santa Barbara (UCSB) and the Universitt Bayreuth (UB) that this proposed work will enable, a clear picture will emerge of how experiments on polyelectrolytes tethered to flat surfaces (at UCSB) connect with highly curved brushes (at UB), common to the surfaces of dispersed colloids. The same physics of polymers and ion confinement is at play in both systems. Many of the practical situations cited above can involve multi-valent ions for which there is much less experimental information and fewer established theoretical principles, than for media comprising mono-valent ions exclusively. Biological buffers, for example, typically contain many ionic species, including multi-valents. Multi-valent interactions, known to have strong effects on polyelectrolytes in solution, as in the condensation of DNA, have been studied very little in their effects on interfacially tethered polyelectrolytes, despite many studies in free solution and the broad biological and technological significance charged interfaces. Polymer chains in tethered assemblies (surface brushes, chains tethered to particles, and highly branched macromolecules) provide an experimental "grip" on the tethered ends of the macromolecules, which enables direct measurement of forces in a way that cannot be done with free linear polymers in solution.
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0.915 |
2009 — 2015 |
Tirrell, Matthew Schlossman, Mark (co-PI) [⬀] Viccaro, P. Mini, Susan Russell, Thomas |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Crif: Facilities: Research Facilities At Chemmatcars: a Synchrotron Resource For Chemistry and Materials Science At the Advanced Photon Source
The Division of Chemistry and the Division of Materials Research at the National Science Foundation, and the Office of Basic Energy Sciences at the Department of Energy provide continuing support to ChemMatCARS at the Argonne Advanced Photon Source under the Chemistry Research Instrumentation and Facilities Program (CRIF). The award provides maintenance, operation and selected upgrades of this unique resource as a national user facility for the chemical and materials science communities. The major techniques supported by the facility include chemical crystallography, surface science, small-angle X-ray scattering and wide-angle X-ray scattering. The instrumentation can be adapted to accept a wide variety of user chambers for specialized sample environments.
This user facility provides a unique high brilliance X-ray resource for the study of surface, interfacial and bulk properties of liquids and solids on length scales ranging from the atomic to the mesoscopic. The facility deals with a wide variety of scientific problems ranging from crystal structure determination to formation of porous membranes to lithium batteries. The research activities enabled by the ChemMatCARS user facility set the pace in adapting synchrotron techniques to best serve the chemistry community; contribute to the development of improved materials, notably plastics, membranes and nano-composites. The facility serves as a training ground for researchers at all levels.
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0.915 |
2010 — 2015 |
Schaffer, David (co-PI) [⬀] He, Lin Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Idr: Nucleic Acid-Lipid Films - Programmable Structural Transitions For Drug Delivery and Regulating Gene Expression @ University of California-Berkeley
1015026 Tirrell
Intellectual Merit:
This interdisciplinary program aims to bring new developments in self-assembled materials to bear on frontier problems in bioactive nucleic acid (NA) delivery and gene expression. Materials comprising nucleic acids and lipids, assembled based on a balance of electrostatic, hydrophobic and hydration forces, form stable, layered films, alternating nucleic acid and lipid layers. Recently published work from our group has shown that this structure can be manipulated in various ways, for example, by changing the temperature or state of hydration, or by varying the molecular weights of the nucleic acids included. This provides a versatile platform of potentially enabling technology to advance and develop new capabilities in gene delivery and the regulation of gene expression. The first aim of the proposed work is to optimize these constructs for the stated delivery applications. Preliminary work included in the proposal demonstrates that nucleic acid delivery, leading to transfection of stem cells, is possible with these constructs. Maximization of this capability will be explored by varying lipid choices (to have the best possible disassembly characteristics and to minimize any toxicity), by including multiple nucleic acids to have the desired structural features, and more importantly, to be able to have simultaneous, multiple transfection ability. The structures and disassembly profiles of all of these constructs will be thoroughly characterized. A second aim of this work, which will be conducted in parallel with the first, is to use these constructs to examine transfection efficiency for mouse embryonic stem cells in culture, using expression of green fluorescent protein as an indicator of efficiency. Stem cells are notably difficult to transfect; our aim is to exploit the high concentration of nucleic acids in our constructs, and the direct physical contact of the cells with the nucleic acid-lipid layers to increase transfection efficiency. A third aim of the work will be to apply our new material delivery vehicles to the delivery of microRNAs. MicroRNAs (miRNAs) are a novel class of small, regulatory non-coding RNA, serving as potent regulators for gene expression at posttranscriptional level. Contact-mediated delivery will be explored to accomplish this goal. The further goal of the third phase of this work is to integrate plasmid DNA and miRNA delivery to reprogram adult cells into induced, pluripotent stem cells. iPS cells have numerous profound scientific and biomedical implications in personalized therapies and platforms for high-throughput screening of pharmaceuticals. The technical challenge with microRNA delivery for reprogramming is not delivery efficiency, per se, but rather sustained delivery to achieve sustained expression over a span of approximately ten days.
Interdisciplinary Nature of the Proposed Research:
The team assembled spans several different disciplines from chemical engineering and materials science, to stem cell and tissue engineering, to the molecular and cellular biology of gene regulation. The proposed work will take a discovery in materials science quite far toward new enabling technology in engineering nucleic acid delivery and gene expression. The connection this team embodies, among chemical and materials engineering, biology and biological engineering, is essential to realize the potential of this new delivery system, both to have the insight into how to optimize the materials involved, and to assure that the biological engineering objectives are achieved in a meaningful way.
Broader Impacts:
An exciting, interdisciplinary development project such as this is an ideal opportunity to bring undergraduate engineering students to the forefront of an important research area. The very nature of this project, spanning three laboratories in chemical, materials and biological engineering, as well as molecular and cellular biology, gives capacity to bring undergraduates with varied interests into participation in this work. The specific plan is to engage two undergraduate students per year, in the summer (six total over the project lifetime), from underrepresented groups as participants in this research. These students will be admitted to the Amgen Scholars Summer Research Program at UC Berkeley. The Amgen Scholars Program is a national program attracting approximately 25 participants each year. Joining this group of 25, the two undergraduate participants will benefit significantly in numerous ways as members of the summer research cohort. They will participate in all program activities including weekly meetings and the poster session and oral presentations at the end of the summer. As a result of these collaborative activities, the undergraduate participants in this project will be fully involved in a broad and comprehensive summer experience.
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0.915 |
2010 |
Tirrell, Matthew |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Effects of the Systemic Environment On Muscle Aging @ University of California Berkeley
DESCRIPTION (provided by applicant): Adult skeletal muscle robustly regenerates throughout adult life but fails to do so in old age. The reason for such a decline in the regenerative potential is not well understood and the relative roles of the changes in muscle cells versus the alterations in their aged environment have not been defined. Recently is has been shown that a young systemic milieu restores the activity of the regeneration-specific Notch pathway and enhances repair of old muscle, suggesting that largely intact regenerative potential of aged satellite cells is not properly triggered in the aged environment. Our most recent data suggest that it is not simply the lack of "positive" systemic factors that causes impaired organ stem cell activation and tissue repair in the old, but that the aged systemic and muscle niches actually inhibit Notch activation and the regenerative potential of both old and young satellite cells. Namely, satellite cells isolated from old muscle or exposed to aged mouse serum in vitro are inhibited in their regenerative capacity and lack Notch activation. Moreover, our preliminary data identifies a molecular mechanism of this age-related inhibition by demonstrating that the reduced regenerative potential of satellite cells in the aged environments stems from excessive TGF-beta/pSmad signaling induced in these cells by their aged niches, which in turn is a result of the elevated levels of TGF- beta-family ligands in aged circulation and muscle tissue. Very importantly, our preliminary results suggest that both myogenic potential and Notch activation can be rejuvenated by attenuation of TGF-beta/pSmad signaling in satellite cells. These studies emphasize high therapeutic relevance of understanding the regulation of adult myogenesis by TGF-beta super-family and of designing the approaches for tunable calibration of TGF-beta/pSmad signaling in muscle stem cells. In order to decipher the age-related role of TGF-beta/pSmad signaling in muscle repair and to progress toward therapeutic applications, it is needed to determine 1) what are the "youthful" positive versus "aged" negative levels of TGF-beta-superfamily ligands in circulation and muscle tissue;2) at what age-related levels TGF-beta/pSmad signaling becomes excessive and "negative" for satellite cell regenerative capacity and 3) how to design a tunable system for a precise "youthful" recalibration of TGF-beta/pSmad signaling in satellite cells. These goals will be approached here in the proposed Specific Aims.
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0.915 |
2014 — 2019 |
Schlossman, Mark (co-PI) [⬀] Lee, Ka Yee Tirrell, Matthew Pink, Maren |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Chemmatcars: a Synchrotron X-Ray National Facility For Chemistry and Materials Research At the Advanced Photon Source
The Division of Chemistry and the Division of Materials Research with support from the MPS Office of Multidisciplinary Activities provides continuing support to ChemMatCARS, a national user facility for frontier research in chemistry and materials science employing synchrotron X-rays at the Advanced Photon Source, Argonne National Laboratory. Various stations at ChemMatCARS serve a broad national and international community of scientists. Research activities address vital societal issues, including the development of new energy sources such as solar-to-hydrogen production, biomolecular materials inspired by biological processes, environmental remediation processes, and new materials and catalysts important for a wide range of industries. The facility serves as a training ground for researchers at all levels and carries out numerous activities to develop and diversify the future STEM workforce.
This user facility provides a unique high brilliance X-ray resource for the study of advanced small-molecule crystallography, liquid surface and interface scattering, and ultra-small to wide-angle scattering from bulk materials. Advanced instrumentation at ChemMatCARS enables forefront research of ordered and disordered solids, liquids and interfaces on the atomic, molecular and mesoscopic length scales over a range of time scales from nanoseconds to minutes. Users of ChemMatCARS take advantage of its unique capabilities to address a wide variety of scientific problems. Research topics include studies of interfacial chemistry important for environmental and life processes, biomolecular materials, metal-organic frameworks for gas adsorption and separation, inorganic materials for catalytic, electronic and magnetic applications, photo-responsive materials for switches, sensors, and energy production, directed assembly for tunable mesoscale structures, and new processes and materials for energy production and storage.
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0.915 |
2015 — 2017 |
Rivers, Mark Tirrell, Matthew Schlossman, Mark [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mri: Acquisition of a Pilatus3 X Cdte 1m For Chemmatcars and Gsecars At the Advanced Photon Source @ University of Illinois At Chicago
This Major Research Instrumentation award to the University of Illinois at Chicago supports the acquisition and implementation of a state-of-the art cadmium telluride (CdTe) pixel array area detector for advanced X-ray synchrotron applications in the areas of chemical, materials, and earth sciences. The instruments will support research at ChemMatCARS and GeoSoilEnviroCARS (GSECARS) the Advanced Photon Source (Argonne National Laboratory). ChemMatCARS and GSECARS are national user facilities with a broad impact on the nation's research and educational infrastructure and serve about 1400 users annually. Studies of materials using this detector will provide the foundation for our scientific understanding of materials at the atomic level. This detector is particularly well suited to the high energy X-ray source at the Advanced Photon Source. Over half of these researchers are students, who are trained in state-of-the-art X-ray techniques. ChemMatCARS and GSECARS conduct workshops and other training, including a focus on training and outreach for women and under-represented minority students. Training the next generation of scientists in the use of the proposed state-of-the-art detector keeps our scientific community up to date and provides them with the experimental tools needed to best address the challenging problems in their research. In addition to Major Research Instrumentation funds from the Division of Materials Research and the Division of Earth Sciences, this award is supported using funds from the Chemistry Division and The Office of Multidisciplinary Activities in the Mathematical and Physical Sciences Directorate.
X-ray detectors are used to record the interaction of X-rays with materials, thus yielding the atomic-level structure of the material. The capabilities of the new detector, the Pilatus3 X CdTe 1M, which include its large active area, high efficiency at high energies, speed, large dynamic range, and low-noise photon counting, will transform crystallography and other measurements at ChemMatCARS and GSECARS. Within ChemMatCARS, the detector will be used primarily by the advanced crystallography station in research areas that include solar energy conversion, photo-excitation, catalysis, hard inorganic materials, metal-metal bonded complexes, and processes within metal organic frameworks. Within GSECARS, the new detector will be used in research to advance knowledge of the composition, structure and properties of earth materials, the processes that produce them and the processes they control. The unique capabilities of GSECARS will continue to allow groundbreaking experiments to be conducted in research areas that include high pressure and high temperature mineral physics in the diamond anvil cell and multi-anvil press, non-crystalline and nano-crystalline materials at high pressure and high temperature, including studies of liquids at conditions that simulate the Earth's deep mantle, and mineral-water interface reactions.
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0.915 |
2017 — 2020 |
De Pablo, Juan (co-PI) [⬀] Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nsf/Dmr-Bsf: Peptide Based Multifunctional Materials For Selective Capture and Release of Nutrients and Contaminants
PART 1: NON-TECHNICAL SUMMARY
Phosphorous is essential to food production. Rising global population is increasing demand for high quality foods and production of plant-based biofuels, causing the rapid depletion of natural phosphorus resources. This non-sustainable sourcing of phosphorus is underscored by the fact that, ultimately, mined phosphate is lost from the food production system as agricultural runoff, livestock manure and food-processing wastes. In addition, phosphate-containing waste streams contaminate natural bodies of water, which leads to a decrease in biodiversity and potable drinking water. Therefore, efforts that advance the separation and recycling of phosphorus are necessary for protecting natural bodies of water and sustaining global food production. This work aims to develop a reversible bio-molecular recognition system that will remove phosphate where it is problematic, recover it, and reinsert it into the global food-production system as a means for enhancing sustainable use of this scarce resource.
PART 2: TECHNICAL SUMMARY A challenge in materials science is the development of materials for selective capture and release of key nutrients (e.g., phosphorous, nitrogen and potassium) and contaminants (e.g., heavy metals, organochlorine pesticides, pathogens). This work aims to develop a novel, optimized, multifunctional material for selective separation of phosphorus based on biologically inspired, peptide amphiphiles with supramolecular phosphate recognition capabilities. The tunable self-assembly properties of these peptide amphiphiles will be used to engineer a system that (1) sequesters phosphorus from model waste streams, (2) enables specific release and reuse of phosphorus, and (3) inhibits non-specific interactions and bacterial growth that can lead to bio-fouling. The stages of this proposed work will progress from design and synthesis of these functional peptides with hydrophobic conjugation, to assembly of these molecules on surfaces and in micellar constructs, to measurement of phosphate binding energetics and kinetics. In parallel with this experimental development cycle, molecular simulations will be aimed at elucidating the phosphate-binding mechanism of the peptide candidates in the experimental work and discovering peptides with improved supramolecular recognition and assembly properties, which can then feed back into the experimental program.
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0.915 |
2019 — 2024 |
Schlossman, Mark (co-PI) [⬀] Lee, Ka Yee Tirrell, Matthew Betley, Theodore Benedict, Jason |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nsf's Chemmatcars: a Synchrotron X-Ray National Facility For Chemistry and Materials Research At the Advanced Photon Source
The Division of Chemistry, the Division of Materials Research and the Directorate for Mathematical and Physical Sciences Office of Multidisciplinary Activities provide continuing support to NSF's ChemMatCARS. This is a national user facility for frontier research in chemistry and materials science employing synchrotron X-rays at the Advanced Photon Source, Argonne National Laboratory. Various stations at NSF's ChemMatCARS serve a broad national and international community of scientists providing some unique capabilities not found anywhere else in the world. Research activities address vital societal issues, including the development of new energy sources, biomolecular materials inspired by biological processes, studies of interactions that help in understanding the rules of life, environmental remediation processes, and new materials and catalysts important for a wide range of industries. The midscale-funded facility serves as a training ground for researchers at all levels and carries out numerous activities to develop and diversify the future STEM workforce.
This user facility provides a unique high brilliance X-ray resource for the study of advanced small-molecule crystallography, liquid surface and interface scattering, and anomalous small angle X-ray scattering. Advanced instrumentation at NSF's ChemMatCARS enables forefront research of ordered and disordered solids, liquids and interfaces on the atomic, molecular and mesoscopic length scales over a range of time scales from nanoseconds to minutes. Users of NSF's ChemMatCARS take advantage of its unique capabilities to address a wide variety of scientific problems. Examples of crystallographic research topics include studies of electron density distributions, disorder in thermoelectric materials, photo-responsive materials essential to capture solar light for energy production and storage, capturing reactive intermediates in photosynthesis models and catalysts, and studying phason strain (face distortion) in quasicrystals under high pressure. Additional illustrations are studies of three-dimensional delta-pair distribution function (3D-delta-PDF) that provides detailed and quantitative information on defects, disorder and lattice dynamics, examination of explosives under extreme conditions, metal-organic frameworks for gas adsorption and separation, inorganic materials for catalytic, electronic and magnetic applications, and ferroelectric assemblies. The synchrotron provides the most powerful probe of molecular and mesoscale structure at liquid/liquid and liquid/surface interfaces which are essential to the understanding interactions between macromolecules (e.g., proteins) and cell membranes that underlie many life processes and provide information to determine the rules of life. This area also provides information on organized assembly of nanoparticles at liquid interfaces with specific optical, catalytic, sensing, and electromagnetic functionalities. The anomalous small angle X-ray scattering (ASAXS) for the study of metal ion distribution near polyelectrolytes, colloids, and nanoparticles from bulk materials. ASAXS is the only technique that can measure the distribution of specific elements within the bulk environment of disordered materials. This is used to study the effect of metal ions on nucleic acids RNA and DNA and to gain understanding and improve separations processes of lanthanides and actinides that is useful in processing radioactive waste.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.915 |
2021 — 2025 |
Tirrell, Matthew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Dmref: Goali: High-Affinity Supramolecular Peptide Materials For Selective Capture and Recovery of Proteins
NON-TECHNICAL SUMMARY
This project is an integrated experimental-computational approach that aims to develop a class of peptide-based supramolecular materials as high-affinity precipitants for non-chromatographic protein purification. The separation and purification of therapeutic proteins from their biological resources are a significant limitation for industrial manufacturing of biologics in terms of their efficiency and cost-effectiveness. Despite the high media cost and limited loading capacity, affinity chromatography remains the most widely used capture method for large-scale industrial protein purification. The rapid growth of upstream titers, due to advancements in mammalian cell culture and continuous process development, has further challenged the efficiency of downstream manufacturing. Affinity precipitation can potentially overcome the chromatography limitations associated with column size and ligand immobilization. In line with the goals of the Materials Genome Initiative (MGI), this project will design, synthesize, and develop self-assembling peptide materials that can specifically bind, selectively capture, and effectively separate proteins from their bio-based resources. In addition, this project will foster new educational and outreach opportunities for students at all levels to participate in STEM research and to experience different laboratory settings that range across academia and industry.
TECHNICAL SUMMARY
This project aims to address the key fundamental challenges in the development of peptide-based affinity precipitants for downstream protein manufacturing. There are essentially three steps in the use of affinity precipitants for protein purification. These are the: (1) selective capture of proteins of interest; (2) binding-induced phase separation from supernatant; and (3) recovery of proteins. The project includes three specific aims, each covering a key step toward the successful development of peptide-based supramolecular immunofibers for non-chromatographic protein purification. The first thrust focuses on the design and synthesis of immunofibers for selective capture of target monoclonal antibodies (mAbs). The second is intended to understand, determine, and optimize the conditions for mAb binding-triggered macroscopic phase separation. The third aim centers on the protein recovery processes and the assessment of system applicability and scalability. Theory and multiscale models will be developed to provide guiding principles for the supramolecular design of immunofibers and the co-assembly strategies to optimize the ligand presentation for maximal protein capture, and to help elucidate the thermodynamic and kinetic aspects of immunofiber assembly and dissociation, as well as the binding-triggered phase separation mechanisms.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.915 |