1989 — 1993 |
Clegg, Dennis O |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Role of a Laminin Receptor in Neuromuscular Development @ University of California Santa Barbara
The basal lamina extracellular matrix that surrounds myofibers has a profound influence on developing and adult neurons and muscle cells, and many of this effects can be attributed to the glycoprotein laminin. The long term goal of this research is to understand how neurons and muscle cells interact with and respond to laminin. Several cell surface laminin receptors have been described bur their specific functions are unclear. The focus of this grant is to determine the function of aspartactin, a newly discovered muscle surface laminin binding protein whose role in development is unknown. Proposed experiments will make use of new and existing antibodies and cDNA clones to characterize the spatial and temporal pattern of aspartactin gene expression, particularly with regard to regulation during myogenic differentiation in skeletal muscle. In addition, a detailed investigation of the interaction between aspartactin with laminin will be completed. Next, the importance of aspartactin in myoblast response to laminin and in myotube assembly of laminin in the basal lamina will be evaluated. The perturbing effects of purified aspartactin, as well as antibodies against aspartactin that block laminin binding, will be examined in a battery of in vitro assays. Function will also be assessed genetically by obtaining mutant cell lines with increased or decreased aspartactin expression. Mutants will be obtained via sense and antisense expression of cloned chick and rat aspartactin cDNAs and by selection using anti-aspartactin antibodies and complement. A phenotype related to altered aspartactin expression will be sought. Knowledge of muscle interactions with the basal laminal will contribute greatly to an understanding of normal development processes that are disrupted during disease. the proposed research should be pertinent to understanding the basic biology that is in disarray in debilitating neuromuscular degenerative diseases. This work may also shed light on how tumor cells pass through basal lamina boundaries during metastasis.
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0.958 |
1994 — 1996 |
Clegg, Dennis O |
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. |
Retinal Receptors For Development Cues @ University of California Santa Barbara
The development of the retina required a complex interplay between retinal cells and the external molecular and cellular cues that regulate their development. The molecular basis of cell-cell interactions in the retina is poorly understood. Insight into these interactions may lead to treatments aimed at regenerating optic nerve function after injury and to a greater understanding of retinal disease resulting from aberrant cell adhesion events. Preliminary results in this proposal describe evidence that an important cell adhesion receptor subunit, previously thought to act only in blood cells, is expressed in developing retina. The presence of this subunit, called integrin alpha 4, suggests that a novel retinal mechanism for cell-cell interactions may be in operations during retinal development. This proposal addresses the function of alpha4 integrins in retinal development. Integrins are a family of transmembrane, heterodimeric proteins that acts as receptors for a broad range of extracellular matrix and cell surface glycoproteins. In lymphocytes and leukocytes, alpha4 integrins acts as bifunctional receptors for both classes of ligand: they mediate cell attachment to a domain in fibronectin and to the vascular cell adhesion molecule VCAM-1. Since fibronectin has not been consistently detected in developing retina, alpha4 may mediate interactions with VCAM-1 or a novel ligand. The first specific aims of this proposal are to determine the range of retinal cells that express alpha4 integrins and VCAM-1. Next, experiments are proposed to define the functions of alpha4 and VCAM-1 in vitro, using function blocking antibodies to perturb cell adhesion and neurite outgrowth. Finally, in vivo experiments are proposed to alter alpha4 expression, by expressing antisense RNA, and to block alpha4 function, by introducing blocking antibodies to define the role of alpha4 integrins in retinal development.
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0.958 |
1997 — 2000 |
Clegg, Dennis O |
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. |
Retinal Receptors For Developmental Cues @ University of California Santa Barbara
The development of the retina required a complex interplay between retinal cells and the external molecular and cellular cues that regulate their development. The molecular basis of cell-cell interactions in the retina is poorly understood. Insight into these interactions may lead to treatments aimed at regenerating optic nerve function after injury and to a greater understanding of retinal disease resulting from aberrant cell adhesion events. Preliminary results in this proposal describe evidence that an important cell adhesion receptor subunit, previously thought to act only in blood cells, is expressed in developing retina. The presence of this subunit, called integrin alpha 4, suggests that a novel retinal mechanism for cell-cell interactions may be in operations during retinal development. This proposal addresses the function of alpha4 integrins in retinal development. Integrins are a family of transmembrane, heterodimeric proteins that acts as receptors for a broad range of extracellular matrix and cell surface glycoproteins. In lymphocytes and leukocytes, alpha4 integrins acts as bifunctional receptors for both classes of ligand: they mediate cell attachment to a domain in fibronectin and to the vascular cell adhesion molecule VCAM-1. Since fibronectin has not been consistently detected in developing retina, alpha4 may mediate interactions with VCAM-1 or a novel ligand. The first specific aims of this proposal are to determine the range of retinal cells that express alpha4 integrins and VCAM-1. Next, experiments are proposed to define the functions of alpha4 and VCAM-1 in vitro, using function blocking antibodies to perturb cell adhesion and neurite outgrowth. Finally, in vivo experiments are proposed to alter alpha4 expression, by expressing antisense RNA, and to block alpha4 function, by introducing blocking antibodies to define the role of alpha4 integrins in retinal development.
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0.958 |
2002 |
Clegg, Dennis O |
C06Activity Code Description: To provide matching Federal funds, up to 75%, for construction or major remodeling, to create new research facilities. In addition to basic research laboratories this may include, under certain circumstances, animal facilities and/or limited clinical facilities where they are an integral part of an overall research effort. |
Extramural Research Facilities Construction @ University of California Santa Barbara
DESCRIPTION (provided by applicant): This application is designed to enhance the quality and increase the quantity of space for National Institutes of Health (NIH)-funded biomedical research at UCSB. A combination of new construction and renovation to create three state-of-the-art research facilities are proposed addressing important, unmet national health priorities in the area of neuroscience, emphasizing neurodegeneration. The research facilities will be: 1) the Alzheimers Research Laboratory (ARL) - proposed is new construction of 10,023 sq. ft. of laboratory and research support facilities in the new Life Science and Technology (LST) Building, which is currently in the final stages of design and review. This will bring together multiple NIH-funded researchers, presently scattered in three locations, much of which is sub-standard space; 2) the Retinal Degeneration Research Laboratory (RDRL)- in the adjacent Biological Sciences II Building, 1,000 sq. ft. of outdated, dysfunctional space will be renovated to accommodate specialized image analysis and specimen preparation for multiple NIH-funded programs focused on retinal disease; and 3) the Core Microscopy Facility (CMF) 1,000 sq. ft. will be renovated to cluster the equipment and support personnel of the Microscopy Facility, presently scattered on three floors in two buildings. Relocation to modern and more functional space will improve efficiency dramatically and allow better management. The impact of this construction will be far reaching, and will include: 1) expansion of research in neurodegeneration; 2) clustering of NIH-funded laboratories sharing common research goals, techniques and equipment; 3) consolidation and improvement of a core facility providing research support for numerous laboratories on campus; 4) free 6,600 sq. ft. of laboratory space for new faculty hires in neuroscience and related biomedical areas; and 5) significantly improve the training environment for future researchers.
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0.958 |
2021 — 2026 |
Pruitt, Beth [⬀] Petzold, Linda (co-PI) [⬀] Clegg, Dennis Manjunath, Bangalore (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nrt-Urol: Data Driven Biology @ University of California-Santa Barbara
This National Science Foundation Research Traineeship (NRT) award to the University of California, Santa Barbara will develop, implement, and test an innovative graduate education model on the theme of Data Driven Biology (DDB). The program's goal is to train a new generation of biological scientists and engineers who can work across disciplines, are fluent in data analytics and experimental methods, and who will advance fundamental research in quantitative biology and bioengineering. Cell and developmental biology are in transition from qualitative observational sciences to quantitative, data-rich fields that leverage modeling and design principles from physics and engineering. Advances in imaging and sequencing technologies, paired with machine learning and computer vision tools, are having a transformative impact on quantitative cell biology. To take full advantage of these technologies, the modern biological engineer needs to be fluent both in the design of biological experiments and in data mining strategies to integrate information across scales (temporal and from genetic/molecular to cellular and tissue scales). DDB seeks to provide students with the breadth to collaborate across disciplines meaningfully and with the depth to answer biological questions with scientific rigor supported by knowledge of and experience with data science approaches. The project anticipates training 70 Ph.D. students, including 30 funded trainees, from doctoral programs in: biological engineering, biomolecular science & engineering, chemical engineering, computer science, electrical and computer engineering, molecular, cellular and developmental biology, mechanical engineering, and physics.
Through DDB, students will learn how to design experiments; acquire and integrate multi-modal, disparate data; and integrate machine learning and computational approaches to extract patterns and meaning from biological data to understand and leverage heterogeneity in stem-cell-derived models. Trainees will be supported by a new curriculum, which will serve as the basis of an emergent Biological Engineering Ph.D. program. Onboarding will include a structured course on seminal research papers and best practices for designing interdisciplinary inquiry. Armed with these training elements, students will be immersed in an in-vivo research experience to conduct hands-on redesign of seminal experiments and to personally implement advanced research methods to test the conclusions of these seminal papers. Students will also engage in co-mentored research rotation projects across diverse labs (experimental and modeling). To support self-reflection, deliberate career planning, and self-efficacy, the program will deploy a three-pronged mentoring plan, including a faculty advisor, peer feedback, and self-assessment through individual development plans. Finally, internships and externships will provide trainees with immersive exchange opportunities across a research network committed to convergent and translational training. This will allow students to experience firsthand how fundamental discovery can ultimately impact applied health applications.
The NSF Research Traineeship (NRT) Program is designed to encourage the development and implementation of bold, new potentially transformative models for STEM graduate education training. The program is dedicated to effective training of STEM graduate students in high priority interdisciplinary or convergent research areas through comprehensive traineeship models that are innovative, evidence-based, and aligned with changing workforce and research needs.
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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