Zhibin Guan - US grants

The proposed research explores new polymeric material design at two interfaces: (1) materials and biology, and (2) materials and catalysts. At the first interface, high value advanced polymeric materials is targeted by mimicking the structures and strategies used in natural materials. The remarkable combined strength and toughness of muscle protein, titin, appears to derive from their modular structures comprising a linear array of domains, in which each domain is held together by secondary forces. Synthetic polymers will be constructed using molecular nanostructures that simulate the modular, multi-domain design of titin. These materials will be tested a both single molecule and bulk material level. The proposed research at the material-catalysis interface is targeted at developing new polymeric materials from simple commercial monomers. Built upon previous successes, new directions are proposed to expand the scope of using catalysts to control polymers with tunable topologies via catalysis, and design of polymers with unconventional topologies via catalysis. In parallel to the synthetic effort, the physical properties and potential applications for the new polymers will be investigated through collaborations with chemists, materials scientists and engineers on campus and at universities nearby.
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The PI's educational goal for the next 4-5years is to build a strong polymer materials program at the University of California at Irvine. The current rapid growth of this campus and the cross campus Materials Initiative provide an excellent opportunity to implement this plan. An effort was initiated to integrate the course offerings in polymer science across a few disciplines to foster interdisciplinary interactions and collaborations. The goal in the undergraduate education is to spark their interests in polymer during introducing the basic concepts and essential knowledge of polymer science. Attention will be paid to interactive teaching methods, the relevance of polymers to our society, and the undergraduate laboratory research. The goal in graduate polymer education is to provide students a solid foundation in polymer chemistry by vigorous treatments of the fundamental mechanism, thermodynamics, and kinetics of each type of polymerization while in the meantime cover major research areas and recent progresses in polymer science. These broad topics will be approached in an interdisciplinary manner and the course format will be developed to encourage greater student involvement. In addition to curriculum development, mentoring also figures prominently in laboratory, classroom, and seminar contexts. The proposed research will increase understanding of the molecular mechanisms for achieving excellent material properties based on structural organization at nanoscale and produce materials with potential biomedical applications. Insight into the relation between the molecular properties of these materials and their performance should allow rational materials designs. The proposed research on catalytic route to new polymer synthesis has the potential to make new polymeric materials with complex topologies from simple and readily available monomers.

DESCRIPTION (provided by applicant): The proposed research investigates a biomimetic modular polymer design as a new strategy to achieve advanced biomaterials. The broad, long-term objective of this research is to develop rational design of biomaterials having high order structures for advanced properties. A specific challenge in biomaterials research is to design a polymer that has a combination of mechanical strength, fracture toughness, and elasticity - three fundamental mechanical properties that are highly desired but usually exclusive to each other in polymeric materials. Many structural biopolymers, such as the muscle protein titin, employ modular domain structures to achieve the combination of these three fundamental mechanical properties in one system. We propose to mimic the modular domain design in synthetic biomaterials. Specifically, we propose to synthesize and investigate biomimetic modular polymers having the following modules: (1) quadruple hydrogen bonding modules, (2) peptidomimetic beta-sheet modules, and (3) small protein modules. Our hypothesis is that the introduction of well-defined modular domain structures into synthetic biopolymers should lead to biomaterials having a combination of mechanical strength, toughness, and elasticity. Whereas numerous biomedical applications can be envisioned for this type of biomaterial, this proposal is focused on developing model polymers having modular domain structures with which to study the fundamental structure-property correlation in synthetic biomaterials. Through the proposed studies the following specific aims will be accomplished: (1) Synthesis and studies on discrete oligomers and polymers using well defined quadruple hydrogen bonding modules; (2) Synthesis and studies on discrete oligomers and polymers containing peptidomimetic a-sheet modules; (3) Synthesis and studies on discrete oligomers and polymers using protein G domain III (PG3) as module; and (4) Systematic investigation on the mechanical properties of the discrete oligomers as well as the high mass polymers made from the above modules at single-molecule, nanoscopic and macroscopic levels.

Dr. Zhibin Guan, Department of Chemistry, University of California - Irvine, is supported by the Inorganic, Bioinorganic and Organometallic Chemistry Program for the development of cyclophane-based late transition metal catalysts for olefin polymerization. First, current and new cyclophane diimine ligands will be optimized for Ni(II) and Pd(II) based olefin polymerization catalysis. This will be done by incorporating electron-donating and withdrawing substituents into the ligands, by changing the backbone structure of the cyclophane diimines; and by introducing fluorinated phenyl rings. Next, Fe(II) and Co(II) complexes of cyclophane tridendate ligands will be explored as olefin polymerization catalysts. This part of the project aims to define any macrocyclic effects of cyclophane ligands on tridendate late transition metal catalyst systems. Finally, late transition metal complexes of the cyclophane ligands will be tested for ethylene homopolymerization and copolymerizations with polar comonomers. The polymerization properties of the complexes will be correlated to the catalyst structures. The trends observed and insights gained will guide further design of better olefin polymerization catalysts.

The broader impacts from the proposed activity include interdisciplinary training of students at multiple levels. Minority and women graduate and undergraduate students will be employed on this project. Additionally, it will impact the polyolefin industry, where the successful development of a commercially viable late transition metal polymerization catalyst would have a tremendous impact.

TECHNICAL SUMMARY:

The objective of the proposed study is to develop highly efficient catalytic synthesis of soft nano-materials having unconventional structures and properties. Nanomaterials are actively investigated for various nanotechnology applications including catalysis, sensors, bio-imaging, drug delivery, and electronics. Among other systems, nanomaterials based on dendritic polymers have received much attention because they have globular shape in solution with molecular dimensions right in the nanometer range. Despite the elegance of many syntheses, the difficulty of preparing dendritic nanomaterials through step-wise synthesis and the limit of ultimate size for regular dendrimers warrant the search of more efficient methodologies for constructing dendritic nanostructures. This proposal details the plan to apply and combine various catalytic polymerization methods to efficiently synthesize soft nanomaterials. In the first part, the unique chain walking polymerization will be combined with atom transfer radical polymerization (ATRP) and ring-opening metathesis polymerization (ROMP) for designing unconventional linear-dendritic block copolymers. In the second part, simultaneous growth of dendritic nanoparticles on multi-sited chain walking catalysts and polymerization of dendronized macromonomer approach are proposed as efficient methods for constructing molecular nano-objects. The physical properties of the synthesized novel soft nanomaterials will be carefully investigated both in the PI's laboratory and through collaboration with other materials scientists in the United States and other countries.



NON-TECHNICAL SUMMARY:

This proposed research is aimed at developing catalytic polymerization methods for efficient preparation of soft functional nanomaterials that are important for various nanotechnology applications including catalysis, sensors, bio-imaging, drug delivery, and electronics. The synthesis will be achieved by efficient transition metal catalyzed polymerization of olefins that are easily accessible from petroleum industry. Successful development of high value nanomaterials from simple olefinic monomers will have significant impact on polyolefin industry. In addition, efficient methods for preparing complex and multifunctional soft nanomaterials may potentially accelerate many nanotechnological developments. The proposed multi-disciplinary research activity will provide excellent training for students in many areas including organic synthesis, organometallic, polymer synthesis and property studies, and nanoscience. This will provide great opportunities to train graduate and undergraduate students, especially for minority and women students.

The objective of this joint proposal is to develop efficient syntheses for new dendritic core-shell nanocarriers and to systematically investigate the effects of molecular architecture on their encapsulation and transport of hydrophobic molecules in aqueous systems. By combining the expertise of the Guan group (UC Irvine, USA) for one-pot synthesis of hydrophobic polyolefin cores with controllable topologies and the Haag group (Freie Universitaet Berlin, Germany) for efficient synthesis of hydrophilic and biocompatible polyglycerol shells, the proposed study intends to develop efficient methodology for the synthesis of core-shell nanocarriers and to reveal basic structure-property information on the resulting new amphiphilic molecular architectures. The understanding of structure-property relationships gained from this study will provide critical insight for designing highly efficient molecular nanocarriers that may find potential applications for ink formulation and drug delivery.

With this award, the Organic and Macromolecular Chemistry Program and the Office of International Science and Engineering are supporting the research of Professor Zhibin Guan of the Department of Chemistry at the University of California, Irvine. This award coordinates with a collaborative award funded by Deutsche Forschungsgemeinschaft (DFG) for Professor Rainer Haag, Freie Universitaet Berlin, Germany. Professors Guan and Haag's research efforts revolve around the development of facile synthetic methods for the preparation of dendritic polymers. Such chemistry will contribute to environmentally benign methods for polymer synthesis as the method is highly efficient. Successful development of the methodology will have an impact on drug delivery for pharmaceutical industries and on dye encapsulation for chemical industries.

[unreadable] DESCRIPTION (provided by applicant): The proposed research is aimed at developing saccharide-peptide hybrid copolymers as a family of fundamentally new versatile polymeric biomaterials. The development of new generations of highly functional, well-defined and "interactive" biomaterials is essential to advance the field of tissue engineering towards a viable clinical reality. Despite this, very few truly novel biomaterials have emerged, with most researchers instead focusing their efforts to modify materials that have been studied for the past 20-30 years. While this approach has achieved certain extent of successes, many of the existing materials suffer from significant limitations and are unable to predictably control cell function. As an alternative, this multi-disciplinary research proposal seeks to develop and test truly novel polymeric biomaterials. Recent breakthroughs in the Guan laboratory led to a series of novel biomaterials derived from peptide and saccharide starting materials. In vitro tests show that the saccharide-peptide hybrid copolymers can be degraded by proteolysis and have low cytotoxicity. Preliminary animal studies indicate these materials do not illicit systemic immune response in rats. These features combined with their versatility and high functionality make these biomaterials promising candidates for interactive biomaterials applications. In this proposal, we will leverage the synthetic chemistry expertise of the Guan laboratory to develop bio-interactive materials, and the cell biology expertise of the Putnam laboratory to investigate these new materials as synthetic extracellular matrix (ECM) analogs. Specifically, we propose to develop efficient synthesis of novel saccharide-peptide hybrid copolymers and test the in vitro and in vivo biocompatibility of these new materials. Through the proposed studies the following specific aims will be accomplished: (1) we will develop efficient and benign synthetic routes for making saccharide-peptide hybrid copolymers and their hydrogels; (2) we will prepare and characterize a series of well-defined hydrogel matrices having precisely controlled chemical and mechanical properties; (3) we will investigate the cytocompatibility of these hydrogel materials as model substrates for cell studies, and address their ability to direct cell phenotype in vitro; and finally (4) we will investigate their in vivo compatibility and potential as cell delivery vehicles. [unreadable] [unreadable] [unreadable]

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polymers are synthesized and crosslinked using tyrosine through the formation of dityrosine. Fluorescent spectrum scans are performed to see if tyrosine and dityrosine can be individually identified within a mixture of digested polymer due to different emission peaks. Further analysis would be needed to quantify the concentration within each mixture.

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)

This award by the Biomaterials program in the Division of Materials Research to University of California Irvine is to study a new family of biodegradable and environmentally responsive saccharide-peptide copolymer-based nanogels as smart nanocarriers for small interference RNA (siRNA) delivery. The recently discovered gene silencing effects of siRNA presents tremendous potential as a new approach in gene therapy for various disease treatments. However, one major barrier for its clinical use is the lack of efficient delivery of siRNA into the target cells. Among different delivery vectors, cationic synthetic polymers are especially promising because of their high structural flexibility and functionalities. A number of polymeric systems have been tested for siRNA delivery, however, their relatively low transfection efficiency and high cytotoxicity warrants further discovery of new safe and efficient delivery systems. Based on previous studies from the PI?s laboratory, the basic saccharide-peptide polymer construct is inherently safe and versatile, offering potential for rational design and optimization. By programming a number of stimuli-responsive features into nanogels, the goal is to combine high stability for nanogel-siRNA complexes (nanoplexes) during extracellular trafficking with efficient release of siRNA once reaching intracellular destinations. Whereas the ultimate goal of this program is to discover truly safe and efficient synthetic vectors for siRNA delivery, the current proposed efforts will be primarily focused on exploring new concept in chemical design and synthesis of nanogel vectors, investigation of chemical-physical properties of siRNA-nanogel complexes, and in vitro siRNA transfection assays using these nanogel vectors.

The discovery of gene silencing capability of siRNA forecasts tremendous therapeutic potential for treating genetic disease using small interference RNA. One major road block preventing it from realization of clinical applications for siRNA technology is the lack of efficient methods to deliver siRNA into cells. This study explores a novel environmentally responsive nanogel approach for efficienct siRNA delivery. The goal of the study is to test a new design concept of nanogel vectors, understand basic structure-property relationship of the nanogel vectors, and ultimately develop safe and efficient synthetic vectors that can potentially have tremendous impact on biotechnological and pharmaceutical industries. In addition, the proposed multi-disciplinary research activity will provide excellent training for graduate and undergraduate students, especially for minority and women students currently working on this project.

Professor Zhibin Guan of the University of California-Irvine is supported by the Chemical Catalysis Program in the Division of Chemistry to explore the scope of a new family of Ru (II) complexes which his lab recently discovered and showed that they have catalytic activity towards olefin insertion polymerization and copolymerization of alpha-olefins with polar monomers. Plans are presented to achieve higher activities through catalyst tuning based on the design of various new ligand architectures, and on a better understanding of the catalytic system and the reaction mechanism. Computational modeling will be conducted to complement the experimental mechanistic and activity studies. The polymerization activities of the complexes will be correlated with the structures of the catalysts. The trends observed and the insights gained will guide further design of better Ru-based olefin polymerization catalysts.

The copolymerization of olefins with polar monomers continues to be a significant challenge and the proposed research has the potential to lead to better routes to functionalized polyolefins and consequently to new polymeric materials with important specialized applications. The proposed research will provide students and postdoctoral researchers with valuable educational experience in organometallic chemistry, polymerization, catalysis, kinetics, and computational science.

TECHNICAL SUMMARY:

The goal of this EAGER award is to investigate a new multiphase strategy for designing strong and autonomously self-healing polymers. Self-healing materials are attractive for many technological applications. Most approaches to self-healing materials either require the input of external energy, or need healing agents (monomer and catalysts), solvent (hydrogels) or plasticizer (rubber). Despite intense research in this area, the synthesis of a strong polymer with intrinsic self-healing ability remains a key challenge. In this EAGER project, a new design of multiphase supramolecular thermoplastic elastomers is proposed to combine high modulus and toughness with spontaneous healing capability. The designed brush polymers self-assemble into complex hard-soft nanophases, combining the strong and tough mechanical properties of nanocomposites with the self-healing capacity of dynamic supramolecular assemblies. In contrast to typical self-healing polymers, the proposed new system spontaneously self-heals as a single-component solid material at ambient conditions without the need for any external stimulus, healing agent, plasticizer, or solvent. The proposed approach to self-healing materials should be generally applicable to a broad range of dynamic multiphase systems, including graft and block copolymers, functional nano-assemblies, and organic-inorganic nanocomposites.

NON-TECHNICAL SUMMARY:

The ability to spontaneously heal injury is a key biomaterial feature that increases the survivability and lifetime of most plants and animals. In sharp contrast, synthetic materials fail after damage or fracture. For decades scientists and engineers have dreamed of developing self-healing polymers to improve the safety, lifetime, energy efficiency, and environmental impact of synthetic materials. In this award an unconventional biomimetic approach is proposed to design multi-phase self-healing polymerc materials that can spontaneously repair themselves under ambient conditions after mechanical damage. Successful demonstration of true self-healing human-made materials could affect the manufacture of elastomers, plastics, and composites, leading to technological advances that would benefit society. The proposed multi-disciplinary research will provide training for graduate and undergraduate students, including underrepresented groups.

DESCRIPTION (provided by applicant): This project brings together the skills of laboratories at UC-Irvine and at City of Hope Diabetes Research Center to design a new family of dynamic dendronized polymers (denpols) for safe and effective delivery of siRNA into pancreatic islets to suppress the islet cell apoptosis and enhance outcome of islet transplantation. Despite the tremendous potential of RNAi for therapeutics, the lack of safe and effective delivery vehicles hampers the clinical promise of siRNA. While considerable efforts have been directed towards the development of non-viral vectors, few systems have progressed into clinical trials and none has received FDA approval. Based on lessons learned from previous studies, here we propose a novel dynamic denpol system for safe and effective siRNA delivery. The denpol design provides an unprecedented opportunity to combine multivalency and conformational flexibility, precise structural control and combinatorial diversity, and multiple dynamic/responsive features to optimize the effectiveness for siRNA delivery. The preliminary results from the collaboration between the PI and co-I's labs have shown that the denpol system exhibits minimal cytotoxicity and high efficiency in transfecting siRNA into both isolated cells (NIH 3T3) and whole rat islets. Built upon the initial successes, three specific aims are proposed to achieve the overall goal of this study. Aim 1 will focus on the design, synthesis, and characterization of a library of denpols with controlled composition and structure. The molecular parameters for the denpols will be systematically and combinatorial varied for optimization. Aim 2 will investigate siRNA complexation and in vitro transfection to isolated cells (NIH 3T3 and rats INS-1 and mouse NIT-1) for the denpols synthesized in Aim 1, from which the optimal structure/composition with minimal toxicity and optimal transfection efficiency will be determined. Finally, in Aim 3, the promising denpol candidates will be investigated for siRNA transfection by exposing isolated islets in culture as well as through ex vivo perfusion of the rat pancreas to determine the optimal denpols and conditions for safe and effective delivery of anti-BBC3 siRNA into islets to suppress islets apoptosis. Islets are chosen as the disease treatment model to evaluate the proposed denpol vectors for two major reasons: (1) RNAi treatment, such as anti-BBC3 siRNA, has great potential to increase islet yield and improve islet transplantation efficiency. There is an urgent need for safe and effective delivery of siRNA to islets to improve islets transplantation outcome; and (2) Islets should serve as an excellent model system to test in vivo transfection efficiency and safety of our denpols, because like most in vivo tissues, islets are composed of tightly bound cells in an orderly fashion. Successful demonstration of this project will introduce a new generation of synthetic vectors for siRNA delivery and improve the outcome of islets transplantation and help developing treatment for type 1 diabetes.

NON-TECHNICAL SUMMARY
Films of semiconductor quantum dots (QDs) are an important emerging class of materials for next-generation solar cells, but the efficiency of cells based on QD films is limited in part by the poor spatial order of the QDs. This project focuses on the development of highly-ordered and electrically-conductive QD films as a new class of electronic materials. With support from both the Electronic and Photonic Materials Program and the Solid State and Materials Chemistry Program in the Division of Materials Research, researchers at the University of California, Irvine (UCI) will make these new materials and study the role of order in charge transport, with the goal of demonstrating greatly improved charge transport in QD films. The project will advance the understanding of transport in functional nanoscale systems, including the role of spatial and energetic order in the emergence of collective mesoscale phenomena such as band formation that depend on strong electronic interactions between nanoscale building blocks. The project will yield new insights into QD self-assembly, interfacial physics, and charge diffusion length, and result in a class of modular, organic-inorganic hybrid QD crystals with transport properties suitable for a variety of QD technologies, including solar cells. Such QD solar cells made by self-assembly from solution can lower the cost of solar electricity and promote solar energy deployment worldwide, with particular benefits to developing communities. The project will also enable a K-12 materials science outreach effort as part of the UCI/Chapman University joint Mathematics, Engineering, Science Achievement (MESA) Program (http://mesa.eng.uci.edu/). The researchers will develop a hands-on QD photophysics MESA program in which students help synthesize QDs and explore their characterization by spectroscopy and electron microscopy. This joint program serves approximately 1,600 elementary, middle and high school students in Orange and Los Angeles Counties, and focuses on promoting STEM education and providing academic enrichment to low-income students from backgrounds with historically low levels of participation in higher education. In addition, several undergraduate students will participate in this research each summer as part of the NSF-funded Chemistry REU and the UCI California Alliance for Minority Participation (CAMP) summer research programs.

TECHNICAL SUMMARY
PbX (X = S, Se, or Te) quantum dot (QD) thin films represent an important emerging class of absorber layers for next-generation photovoltaics (PV). Remarkable progress has been made in QD PV over the past several years by replacing the long, electrically insulating oleate ligands on as-made PbX QDs with short organic molecules or inorganic ions. Unfortunately, these ligand treatments destroy medium and long range order in the QD films. Partly as a consequence, charge transport is limited to sequential phonon-assisted tunneling, resulting in low carrier mobility, short carrier diffusion lengths, and limited photocurrent from QD devices. One exciting prospect is to assemble QDs into electronically coupled, conductive superlattices (crystals of QDs) in which transport can occur via domain-delocalized states or Bloch-type extended states (mini-bands). Mini-band transport in QD superlattices could yield much larger carrier mobility and diffusion length. With support from both the Electronic and Photonic Materials Program and the Solid State and Materials Chemistry Program in the Division of Materials Research, researchers at the University of California, Irvine will replace the oleate ligands of PbX QDs with conjugated organic "molecular wires" to fabricate a new class of conductive PbX QD hybrid superlattice nanocomposites (HSNs) composed of QDs interconnected with molecular wires. The molecular wires will provide excellent superlattice order, tunable HOMO and LUMO levels, strong electronic coupling via barrier lowering, and large inter-QD spacing that is favorable for superlattice crystallization and the adsorption of co-ligands to passivate surface states. The impact of superlattice order on charge transport, carrier mobility, and diffusion length will be studied using an array of electrical and spectroscopic techniques. The main fundamental goal of the project is to elucidate the degree to which and the mechanisms by which superlattice effects enhance carrier mobility and diffusion length in QD films, while the main applied goal is to make HSNs with minority carrier diffusion lengths of at least 1000 nm, which would enable nearly perfect charge collection and very high conversion efficiency from QD PV.

Technical:
The goal of this project is to understand the basic physiochemical properties of a new bolaamphiphile (bola) vector system for siRNA delivery and to design new pH-responsive bolas for improved siRNA delivery efficiency. Despite the tremendous potential of RNAi for therapeutics, the lack of safe and effective delivery vehicles hampers the clinical promise of siRNA. Recently the PI's lab has demonstrated a new design of bolaamphiphiles as promising synthetic vectors for siRNA delivery. The bolas show high efficiency and low cytotoxicity for intracellular siRNA delivery, and fluorocarbon bolas also show excellent serum stability. Despite the excellent performances for bolas, many fundamental questions remain unanswered. This project details PI's plans to address several key questions for this new delivery system. The first major aim of the study is to combine both experimental and computational studies to understand the fundamental properties of bola/siRNA complexes, such as the structure and morphology of the complexes, binding affinity and stability of the complexes, as well as how do they interact with serum and membranes. The fundamental insight gained in the first aim will enable to design more effective bola vectors for siRNA delivery. In the second aim PI proposes a specific design of acid-labile bolas for improving the efficiency for siRNA transfection. The proposed multi-disciplinary research activity will provide students excellent training in many areas including organic/polymer synthesis, biomaterials, nanomaterials, and biology. This will provide great opportunities to train graduate and undergraduate students, especially for minority and women students currently working on this project. The PI is also strongly committed to various K-12 outreach programs that are aimed to excite the younger generation with science and to enhance general public understanding and appreciation of chemical sciences and technologies.


Non-technical:
RNA interference (RNAi) technology has demonstrated tremendous utility both for fundamental biological research and for disease treatments. The high potency and specificity of gene silencing induced by small interfering RNA (siRNA) makes this technology particularly promising for treatment of various diseases including cancer, viral infections, obesity and diabetes. One major roadblock preventing it from realization of clinical applications for siRNA technology is the lack of efficient methods to deliver siRNA into cells. This study explores a novel molecular delivery system for safe and efficienct siRNA delivery. The goal of this project is to understand the basic chemi-physical properties of a new molecular delivery system for siRNA delivery and to design new stimuli-responsive delivery molecules for improved siRNA delivery efficiency. Ultimately, the knowledge gained from this study will facilitate the development of safe and efficient siRNA delivery vectors that can have tremendous impact on biotechnological and pharmaceutical industries. In addition, the proposed multi-disciplinary research activity will provide excellent training for graduate and undergraduate students, especially for minority and women students currently working on this project.

This award provides support for the travel and conference registration fees of students and young investigators as participants in the 2018 Gordon Research Conference Bioinspired Materials, in Les Diablerets, Switzerland, June 24 - 29, 2018. The meeting will allow young investigators to network with establish researchers to discuss cutting edge research about new ideas and future concepts of how to harness or mimic designs and the methods used in nature to achieve them. The overarching goal of this research is to develop a fundamental understanding of the synthesis, directed self-assembly and hierarchical organization of natural occurring materials, and uses this understanding to design new synthetic materials whose structure, properties and function mimic those of natural materials or living matter.

This Gordon Conference will bring together researchers in biomedical engineering, materials science, synthetic biology, genetics, and clinical medicine to discuss the cutting edge of research in the area of new bioinspired artificial materials that are exquisitely developed for high functionality in specific applications. This is a cross-disciplinary conference, designed to build bridges between fields to advance science and engineering in this area. In particular, the conference will focus on fundamental understanding of how particular materials should be designed to be "symbiotic" with biological entities and how to get similarity in functioning of biomaterials with their living counterparts. The conference will include a broad range of researchers, from graduate students and post-doctoral trainees to world leaders in this area, to disseminate the latest advances and develop connections to advance this key field of research moving forward. Award funds will be used to support students and trainees so that they can present their research and develop the research network necessary to advance both science and their careers.

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.

Living systems rely on the energy-fueled assembly of biological building blocks such as proteins to enable vital biological functions including cellular transport, cell migration, division, and shape change. These self-assembly processes in Nature have inspired the design of synthetic systems driven by chemical fuels. The research group of Professor Zhibin Guan at the University of California, Irvine (UCI), aims to develop a general and biocompatible strategy for the self-assembly of active materials that mimic biologically-active materials. Towards this goal, his group conducts research to gain a better understanding of the processes of chemically-fueled assemblies. The research group also seeks to uncover general rules that enable predictive design of self-assembled materials. Such materials may have properties that include being adaptive, self-healing, and autonomous, offering the opportunity to seamlessly interface man-made technologies and biological systems. Students at all academic levels, including minority and women students, participating in this project gain broad training and experience in chemical synthesis, materials chemistry and materials physical property studies. In addition, Professor Guan works with the UCI Mathematics, Engineering, Science Achievement (MESA) Program to develop a module that focuses on dynamic materials for a K-12 chemistry/materials science outreach effort.

Dissipative self-assembly is an out-of-equilibrium process in which consumption of a chemical fuel drives the self-assembly of materials. In living organisms, the transient self-assembly of actin networks and microtubules fueled by adenosine triphosphate (ATP) and guanosine triphosphate (GTP) is at the heart of many cellular processes. While such self-assembly is common in Nature, relatively few synthetic systems of chemical-fueled dissipative assembly have been developed. The general toxicity of the chemical fuels and harsh conditions used in current man-made designs also limit their applications. To address these issues, Professor Guan's research group investigates new mild, biocompatible chemical reactions to control the self-assembly of active materials. In the first aim of this project, the reaction kinetics, redox chemical networks, and emergent properties of a model system are carefully investigated to understand and improve control of the assembly process. The second aim focuses on demonstrating the scope of the approach developed by applying this strategy to various precursors (e.g., cysteine-containing peptides). The last aim seeks to develop a novel approach that is based on photoredox chemistry to fuel an active assembly system.

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.

Nontechnical Summary:
This project develops a new molecular delivery system for enabling the CRISPR-based genome editing technology. CRISPR-based genome editing technology can precisely add, delete, and ?correct? genes in vitro or in vivo; therefore, it holds tremendous potential for therapeutic applications and is actively being pursued for addressing a wide range of human diseases ranging from hereditary diseases, cancer, to diabetes. However, one major obstacle to implementing this technology is the lack of safe and efficient delivery systems that can effectively transport the required molecular machinery into cells to execute genome editing. To address this challenge, this project proposes the design, synthesis, and investigation of a series of delivery molecules made from natural amino acids and peptides. These compounds will be evaluated for their efficiency and safety for delivering two pieces of RNAs into cells for performing CRISPR-based genome editing. Structure-function studies will shed light on important design principles for effective molecular carriers. The proposed interdisciplinary research activities also provide excellent trainings to students at various levels, ranging from K-12, undergraduate, to graduate students, especially women, underrepresented minority students, and those from institutes with limited research opportunities.

Technical Summary:
The goal of this project is to develop a new synthetic delivery platform for RNA-based CRISPR and conduct fundamental structure-property studies on the new delivery system to gain critical insights for the design of new gene delivery vectors. CRISPR/Cas9 gene editing offers a tremendous potential for therapeutic applications and is actively being pursued for addressing a wide range of human diseases. However, one major obstacle to implementing CRISPR-mediated genome editing is the lack of safe and efficient delivery vehicles. The PI lab recently developed an innovative design of bioreducible dendronized polypeptides (BDPs) that show high efficiency for co-delivery of Cas9 mRNA and gRNAs. It is proposed that further investigation of this system will generate a new platform delivery system that can effectively and safely co-deliver CRISPR/Cas9 mRNA and gRNA into various cells. Furthermore, capitalizing on BDP?s well-defined molecular structure, we propose to conduct fundamental structure-property studies on the BDP system with the aim to gain critical insights for the design of new gene delivery vectors. If successful, the proposed study will provide a new, general, and biocompatible delivery system for CRISPR technology and offer critical insights for guiding the design of new gene delivery systems. The research and broad impact activities will provide holistic trainings to students at various levels, ranging from K-12, undergraduate, to graduate students, especially women, underrepresented minority students.

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.

Nontechnical Abstract: The Materials Research Science and Engineering Center (MRSEC) at the University of California, Irvine (UCI) builds on UCI?s strengths in multidisciplinary science and engineering research to establish a major research hub for materials discovery and innovation in the Southern California academe-industry eco-system. The primary mission of this MRSEC is to establish foundational knowledge in materials science by developing new classes of materials that offer unique and broad functionalities. The MRSEC comprises two Interdisciplinary Research Groups (IRGs), each working in close collaboration to address Grand Challenges in national defense and human health. The first IRG aims to create materials which exhibit unprecedented physical properties, such as the ability to withstand extreme environments having applications in national defense. The second IRG team is addressing dynamic, responsive soft materials that are in essence living electronic materials serving as an interface with living systems for healthcare applications. Through seed projects, the UCI MRSEC engages new participants in exciting new research directions. It attracts a diverse group of scientists, including women, underrepresented minority groups, and persons with disabilities, from across the nation and trains future leaders at all academic and professional levels to address critical societal challenges. This MRSEC?s integrated activities?including novel materials research, partnerships with industry and national laboratories, entrepreneurial innovation, career development, and mentorship?are enabling a transformative long-term impact on fundamental science, advanced applications, and workforce development.

Technical Abstract: The UCI MRSEC combines an experimental, computational, and theoretical framework pursuing atomic- and molecular-level design and control of structure and dynamic response through two Interdisciplinary Research Groups (IRGs). IRG 1 investigates the atomic-level structure, chemistry, thermodynamics, and kinetics of interfaces in an emerging class of Complex Concentrated Materials (CCMs) that exhibit exceptional properties such as high strength, ultra-low thermal conductivity, and extremely large dielectric constants. Understanding their structure-property relationships guides design and processing of next-generation structural and functional materials. IRG 2 investigates dissipative self-assembly strategies to understand fundamental charge-matter interactions, with the goal to produce supramolecular ?living? materials. Development of conductive active materials, where assembly is fueled by chemical, electrical, and other stimuli, provides the intellectual framework for a new class of living electronic materials for bio-interfaces and biological computing. The research team leverages state-of-the-art electron microscopy facilities within the Irvine Materials Research Institute and pursues instrumentation innovations to characterize atomic-scale structure and dynamic properties. Multifaceted education, outreach, and collaborations with industry, national laboratories, and nonprofit organizations allow this MRSEC to achieve significant, long-term impact with the targeted scientific advances. This impact includes technological innovation, workforce development, and boosting of the regional and national economy. Synergistic activities provide holistic training of diverse junior scientists at all stages, from K-12, undergraduate, and graduate students to postdoctoral scholars and untenured faculty, further fostering inclusive excellence in STEM.

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.