2016 — 2017 |
Liu, Ming Yan, Ruoxue [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Eager: Understanding Photochemical 2h-1t Phase Transition in Monolayer Mos2 @ University of California-Riverside
Non-technical Description: Ultra-thin transition metal dichalcogenides (TMDs) materials are promising candidates for flexible, low-power and transparent electronics and optoelectronics. Manipulating the atomic arrangements, referred to as crystal phases, can transform TMDs from semiconducting to metallic materials, which is a promising way to improve the overall device performance and/or to attain new functionalities. The current phase-engineering methods either rely on expensive and hostile chemicals or are incompatible with large-scale manufacturing. This project aims to develop a novel photochemical approach, which is controllable, scalable, low-cost, environmentally benign and compatible with electronic device fabrication, to induce phase-change in molybdenum disulfide. The research advances the state of knowledge of the phase-change mechanisms in TMD materials and explores the potential of TMD materials for applications in wearable electronics, foldable displays and lightings, and advanced integrated medical devices. The research effort is integrated with education and outreach activities, including training students in TMD materials, organizing a summer science camp and research internship programs for high school students that are traditionally underrepresented in the STEM field.
Technical Description: This project proposes a novel photochemical concept for phase transition in monolayer molybdenum disulfide to address the pressing need for performance improvement in 2D-TMD based electronic/optoelectronic devices. The goal of this EAGER project is to understand photochemically induced 2H to 1T phase transformation in monolayer molybdenum disulfide and to establish processing-structure and structure-property correlations. In pursuit of this goal, the project objectives are to (1) validate the phase change mechanism through systematic characterizations of photo-chemically formed hetero-phase molybdenum disulfide and evaluate the controllability of the transition by varying processing parameters; (2) investigate the stabilization mechanism of the metastable metallic phase for improved device reliability; and (3) evaluate intriguing optical and electrical properties of phase-engineered molybdenum disulfide. Combined approaches of advanced structural characterization, optical analysis, device fabrication and electrical measurements are used in this research to gain fundamental understandings of the phase-change mechanism and the phase-engineered 2D-TMD materials.
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0.942 |
2016 — 2019 |
Arvan, Peter [⬀] Liu, Ming Qi, Ling (co-PI) [⬀] Tsai, Billy (co-PI) [⬀] |
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. |
High Quality Proinsulin Folding Requires Erad of Proinsulin @ University of Michigan At Ann Arbor
ABSTRACT Inadequate insulin secretion triggers diabetes. Normally, pancreatic ß-cells synthesize more than 300,000 molecules per minute of the insulin precursor, proinsulin, and these molecules must rapidly fold before their export from the endoplasmic reticulum (ER) ? for eventual processing to insulin. Unfortunately, proinsulin folding in the ER always leaves a small subset of misfolded proinsulin molecules (in particular, those forming mispaired disulfide bonds) that can attack ?bystander proinsulin?, triggering ?-cell ER stress, as occurs for the ~30 different INS gene coding sequence mutations in patients suffering from the autosomal dominant Mutant INS-gene induced Diabetes of Youth (MIDY). Significantly, islet ?-cells of individuals with wild-type INS genes also have proinsulin misfolding. In this multi-P.I. R-01 proposal, the applicants' central hypothesis is that normally, the amount of misfolded proinsulin is kept at sub-threshold levels by active ER-associated degradation (ERAD) of proinsulin that prevents excessive accumulation of misfolded proinsulin forms. Failure of efficient ERAD allows the low-level misfolded proinsulin to accumulate and trigger many of the same phenotypes seen in MIDY. Thus ? ironically ? efficient ERAD of proinsulin (in one subset of molecules) is actually coupled to proper folding of proinsulin (in another subset of molecules). Thus, ?--cell secretory capacity depends on the efficiency of ERAD. If correct, then if proinsulin ERAD should become impaired, misfolded proinsulin may accumulate, triggering pancreatic ?-cell dysfunction. Remarkably, our preliminary data establish that ?-cell-specific knockout of the ERAD gene product, SEL1, triggers a dramatic reduction of islet insulin, accompanied by a striking intracellular accumulation of proinsulin in ?-cells. As a consequence of diminished insulin production, mice with ?-cell SEL1 deficiency are predisposed to diabetes. To our knowledge, no other groups have pursued ?-cell ERAD as the critical homeostatic regulator of proinsulin quality control. We wish to define and quantify the molecular pathways regulating this process, and study the process in physiologically relevant diabetes models, including human islets. The group is uniquely qualified to address this central premise: Dr. Tsai is an expert in molecular mechanisms of protein retrotranslocation for ERAD; Dr. Qi is a leader in the development of whole animal models that can directly test the pathophysiologic role of ERAD in tissues; Dr. Liu is a world's leader in preproinsulin translocation across the ER membrane and along with Dr. Arvan, they have elucidated our current molecular understanding of the pathogenic mechanism underlying MIDY. The focus on disposal of misfolded proinsulin is the critical nexus shared by all of us. A more complete understanding of the molecular steps leading to ß-cell failure is critical to the development of new therapies for diabetes. With this in mind, we believe that work proposed by this group will be paradigm- shifting for the field.
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0.945 |