1997 — 2003 |
Raible, David W |
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. |
Regulation of Neural Crest Development @ University of Washington
DESCRIPTION (Adapted from the applicant's abstract): The investigator's long-term goal is to understand how neural crest cells become different from one another, and generate such distinct cell types as neurons, glia, pigment cells and cartilage. Understanding at the molecular level how cells become specified is not only important for determining the proper construction of complex structures such as the nervous system, but is critical for understanding what goes awry in birth defects, or what happens when cells lose growth control in cancer. Understanding of the events leading to the formation of a functioning nervous system will also be important in designing strategies promoting recovery of function. The investigator proposes a positional information model for cell fate determination within the zebrafish cranial neural crest. Cells in different mediolateral positions have different fates: cells located medially generate pigment cells while cells positioned laterally form neurons and glia. The investigator proposes that expression of wnt1 and wnt3a in the dorsal neural tube acts as a medial signal to promote pigment cell fates and inhibit neural cell fates. Expression of BMP2 lateral to the neural crest, and the BMP inhibitor chordin medial to the crest, sets up a lateral signal that opposes the wnt signal. The investigator will test the role of BMP in neural crest specification by injecting individual cells with mRNA encoding activators and inhibitors of BMP signaling and following their development in vivo. In his model, cells located in different positions respond to distributed signals by turning on specific transcription factors that direct the subsequent steps of differentiation. The investigator proposes that the nacre gene, initially identified in a genetic screen for neural crest regulators, acts as such a transcription factor to initiate melanogenesis at the expense of neurogenesis. To test these ideas, the investigator will determine if nacre is sufficient for melanogenesis and whether it is a direct downstream target of wnt signaling. The striking coincidence of lateral neural crest cells that produce neurons and neuron-forming placodes has led the investigator to hypothesize that these cells may be part of the same field, and may thus respond to the same mediolateral signals. The investigator proposes to test this idea by producing a detailed fate map of a putative "placode field" and directly compare it to the neural crest fate map. He will test whether BMP2 plays a role in distinguishing between neural crest and placode.
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1 |
2003 — 2006 |
Raible, David W |
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. |
Cell Fate Regulation by Transcriptional Repression @ University of Washington
DESCRIPTION (provided by applicant): As development proceeds, cells acquire new fates so that they can carry out their proper function within the organism. Conventionally, cell fate specification has been thought of in terms of the activation of transcription factors that subsequently activate cell type specific genes. In this proposal we examine a role for a winged-helix transcriptional repressor, foxd3, in zebrafish neural crest cell fate choice. We hypothesize that foxd3 is involved in cell fate choice not by activating genes for particular cell types but instead by preventing expression of genes involved in acquisition of other fates. We propose that foxd3 specifically represses the bHLH transcription factor mitfa, which is necessary for melanoblast specification. We will address this hypothesis with the following aims: 1. We will test the hypothesis that mitfa is transiently transcribed in glial-pigment cell progenitors, and subsequently repressed in non-melanogenic cells. We will compare the expression of pigment cell markers to the expression of GFP mRNA driven by the mitfa promoter in transgenic animals, and will construct a transgenic line using a fluorescent reporter that acts as a timer to distinguish when transcription and translation occur. 2. We will test the hypothesis that foxd3 represses mitfa expression. We propose to: identify foxd3 binding sites in mitfa promoter, and test whether foxd3 and mitfa are co-expressed. 3. We will test the hypothesis that foxd3 regulates neural crest cell fate decisions by regulating mitfa. We will test the effects of foxd3 on neural crest cell fates by overexpression or antisense morpholino knockdown within the whole embryo and within individual neural crest cells, and test foxd3 loss/gain of function in the context of the mitfa and c-kit mutant backgrounds. These experiments will shed light on the differentiation of a possible common glial/melanoblast precursor and lead to understanding how abnormal development of this precursor might underlie congenital tumors.
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1 |
2003 — 2020 |
Raible, David W Rubel, Edwin W (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. |
Genetics of Zebrafish Hair Cell Toxicity @ University of Washington
DESCRIPTION (provided by applicant): The vast majority of hearing and balance impairments are thought to be due to death of sensory hair cells, the receptor cells of the inner ear. These cells are unusually metabolically active and hypersensitive to damage from overstimulation, some therapeutic drugs and environmental toxins, and aging. However, there is enormous variability in structural and functional outcomes of these challenges to the inner ear among both humans and laboratory animals, and a large number of mutations either directly influence the viability of hair cells, or alter susceptibility to ototoxicity. The goals of the research program proposed herein are: A) to better define the cellular and molecular cascades that control hair cell death and survival following exposure to potentially ototoxic agents;B) to use the genetic potential of the zebrafish and the accessibility of the lateral line neuromasts to identify and characterize genes that influence the viability of hair cells when challenged by ototoxic agents;and C) to employ the lateral line system to rapidly screen for small molecules/drugs that protect against damage. Four groups of experiments are proposed: 1) We will molecularly characterize 5 already identified mutations that confer resistance to aminoglycoside antibiotics;2) We will identify distinct pathways resulting in hair cell death using chemical and genetic modifiers of hair cell death;3) We will screen for new genes and drugs that alter the response to aminoglycosides;and 4) We will determine to what degree our findings from the zebrafish lateral line system extend to mammalian systems. In the US, over 31 million adults have trouble hearing. Our research will reveal how the sound-sensing cells of the ear are damaged, identify genes that may underlie the variability in hearing loss, and find drugs that may help in its prevention.
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2006 — 2009 |
Raible, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Fgf Regulation of Zebrafish Lateral Line Development @ University of Washington
Abstract
Mechanisms that regulate developmental processes during organogenesis are complex. The zebrafish lateral line is an excellent system to study these processes since it is easily accessible for observation and manipulation. Sensory hair cells of the lateral line are positioned on the surface of the body to detect flow of water. Hair cells are deposited along the body by a migrating cluster of about 100 cells called the primordium that originates from a cranial placode. This proposal will test the roles of Fibroblast Growth Factors (Fgfs) in lateral line development, through genetic and embryological manipulation. Preliminary data reveal that Fgf signaling is critical for lateral line patterning. In Aim 1, the expression of Fgfs and Fgf signaling components within the lateral line will be carefully documented. In Aim 2, the roles of Fgf in the migration of the lateral line primordium will be explored. Using a transgenic line where Fgf signaling is conditionally inactivated by expression of a truncated Fgf receptor, the time and location of required Fgf signaling will be determined. In Aim 3, the effects of blocking Fgf10 on migration, patterning and proliferation will be documented. Antisense morpholino oligonucleotides will be introduced into embryos to characterize the role of Fgf 10 on neuromast deposition. The combined roles of Fgf10 with Fgf3 will also be examined. The proposed studies examining the roles of Fgf signaling in lateral line development have the opportunity to reveal fundamental mechanisms underlying coordination of cell proliferation, migration and differentiation during embryogenesis. The proposed studies may shed light on the similar roles of Fgf signaling in regulating migration and proliferation during angiogenesis and tumorigenesis. There is significant variation amongst aquatic vertebrates in the patterning of the lateral line organs, and defining molecular mechanisms that regulate patterning will allow future study that may determine factors that influence this variation. Understanding the mechanisms that regulate lateral line development may also reveal similarities with the development of other placode-derived structures including the auditory and vestibular organs.
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0.915 |
2007 — 2008 |
Raible, David W |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Genetic Analysis of Hair Cell Regeneration in Zebrafish @ University of Washington
[unreadable] DESCRIPTION (provided by applicant): Mechanosensory hair cell loss is the leading cause of human hearing and balance disorders. While new hair cells do not regenerate in humans, this process is common in other animals. Moreover, in some animals there is constant production of hair cells throughout their life, requiring a steady supply of new hair cell precursors. In this R21 application, we propose experiments to identify self-renewing precursors within the zebrafish lateral line system, and screen for mutations that alter precursor function. Lateral line mechanosensory hair cells share many properties with the inner ear, but since they are located on the body surface, they are easily accessible to visualization and manipulation. These experiments take advantage of the zebrafish system, including their rapid development, established genetics and advancing genomics. We propose 2 aims: to identify mutations that alter hair cell regeneration as a first step to uncovering the molecular regulation of this process, and to identify hair cell precursors within the adult lateral line and determine whether they have the self-renewing properties of stem cells. The proposed exploratory research should establish the zebrafish lateral line as a model for hair cell regeneration, and develop genetic resources that will be useful to the research community. Mechanosensory hair cell loss in humans, the leading cause of hearing and balance disorders, is irreversible. In contrast, hair cells regenerate in other animals. Understanding the regulatory mechanisms behind successful regeneration will influence strategies towards recovery of function in humans. [unreadable] [unreadable]
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2007 — 2011 |
Raible, David W |
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. |
Genetic Regulation of Neural Crest Neurocongenesis @ University of Washington
DESCRIPTION (provided by applicant): How distinct cell fates are generated from initially homogeneous cell populations is a fundamental question in developmental neurobiology. The neural crest is one such cell population that is capable of producing an incredible array of derivatives. Cells as different in function and form as the pigment cells in the skin or the neurons and glia of the peripheral nervous system are all derived from neural crest. Studies to understand the specification of a specific cell type, dorsal root ganglion (DRG) sensory neurons, are proposed. The transcription factor Ngn1 is critical for DRG specification. We have developed a transgenic line where DRG precursors are marked by GFP expression regulated by ngnl control elements. We propose to use this line to understand the regulatory pathways involved in DRG specification. We will examine the roles of the Notch signaling pathway in regulating sensory neuron cell number. We will also follow the addition of new DRG neurons from latent precursors long after neural crest formation has ceased. In addition, a forward genetic screen has identified three mutations that alter DRG development. We propose to characterize the locus of mutation action and identify the underlying molecular lesions. Finally, we propose a new screen to identify additional mutations. Understanding sensory neuron development may eventually help in the design of therapies for improving function in patients affected with neurodegenerative diseases, diabetes-related sensory neuropathy, and pain disorders.
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2010 — 2014 |
Raible, David W Stone, Jennifer S. |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Imaging @ University of Washington
Modern cellular and molecular biology relies on high-resolution analysis of spatiotemporal distributions of structures and molecules in live and fixed specimens. For the past 9 years, microscopic imaging for researchers in communications disorders at the University of Washington (UW) has been greatly enhanced by the NIDCD P30 Microscopic Imaging Core (Core C). These investigators have a long history of active interactions that have resulted in many co-authored publications and collaborative grants. Core C has facilitated microscopic imaging capabilities by increasing investigator access to modern methods for image acquisition and processing, expanding the breadth and efficiency of tools and experimental approaches for digital imaging, and increasing scientific interactions among its users. The major facility for this Core, the Digital Microscopy Center is based in the Center on Human Development and Disability (CHDD), in space adjacent to the Virginia Merrill Bloedel Hearing Research Center (VMBHRC). It includes 5 microscopes, 3 imaging workstations, and an advanced data archival system. The equipment, staffing, and day-to-day operation of this facility are possible through a partnership between the CHDD and the VMBHRC that has proven highly successful. Additional imaging facilities for core users are located outside the Digital Microscopy Center. The most significant and essential contributions made by this core are the salary support for the Staff Scientist, Glen MacDonald, and full coverage of usage fees for several microscopes for Core users. Mr. MacDonald has 23 years'of experience with fluorescent labeling, microscopic imaging, and digital image processing. For the last 9 years, he has managed this imaging facilities, upgraded its capabilities, and provided training for investigators, staff, and students. He has advanced labeling and imaging techniques, helped to purchase and maintain state-of-the-art imaging hardware and software, and established rigorous data backup systems. His efforts are invaluable to the core. In addition, the P30 has covered costs for microscope usage that would otherwise be highly taxing to individual research programs.
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2010 |
Raible, David W |
S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
Intelligent Imaging Spinning Disk Confocal Microscope @ University of Washington
DESCRIPTION (provided by applicant): The requested spinning disk microscope will allow the core researchers at the University of Washington to advance research using live imaging technologies. The spinning disk microscope allows rapid sampling of fluorescent images in living specimens. Because the speed of image capture is increased on spinning disk systems, very rapid processes can be imaged at high resolution, including vesicular trafficking, changes in mitochondrial dynamics, changes in intracellular ion concentrations, fusion of membranes, cytoskeletal remodeling events, rapid movement of cells, etc. Minimizing light exposure is critical for many live applications to reduce potential phototoxicity. Spinning disk microscopes subject specimens to much lower light levels than conventional confocal microscopes, and are thus well suited for live imaging. Projects supported by the instrument include the understanding of developmental cell fate, which will have critical impact on our understanding of birth defects and other genetic diseases, the molecular basis of hearing loss, and a detailed study of the host-pathogen interactions leading to tuberculosis, a debilitating and lethal infection of children and adults.
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2010 — 2014 |
Raible, David W |
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. |
Screens For Modulators of Hair Cell Regeneration @ University of Washington
DESCRIPTION (provided by applicant): Hair cells are sensitive to environmental insults such as excessive noise or chemical exposure, resulting in their death. Unfortunately, their loss in humans is irreversible. In this application, we propose to use the zebrafish mechanosensory lateral line system to study the regulation of hair cell regeneration. Lateral line hair cells share cellular and molecular properties with hair cells of the inner ear, yet are easily accessible to visualization and manipulation. We propose two screens: to search for mutations that alter hair cell regeneration and to identify small molecule regulators of regeneration. Our preliminary studies show that both screens are feasible. In initial screens, we have identified 8 mutations that alter regeneration and two compounds that enhance hair cell replacement. We propose to characterize in detail the mechanisms by which hair cell regeneration is altered by these genetic and small molecule modulators. We will also map mutations to begin identification of the molecular lesions that underlie mutant phenotypes. These studies will help us understand the regulatory pathways that control zebrafish hair cell regeneration, and may reveal the steps altered in mammals that no longer allow regeneration to occur.
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2011 — 2015 |
Raible, David W Rubel, Edwin W [⬀] Simon, Julian A |
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. U01Activity 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. |
Drug Discovery For the Prevention of Hearing Loss @ University of Washington
DESCRIPTION (provided by applicant): This research program is designed to test the efficacy of candidate drugs, for protection against inner ear receptor cell (hair cell) loss and hearing loss resulting from systemic treatment of patients with gram- negative antibiotics. Loss of inner ear hair cells is the leading cause of hearing loss and balance dysfunction, affecting approximately 31 million Americans. The candidate drugs under investigation will be analogs of PR0T01, a small molecule, drug-like compound discovered using a well-characterized chemical screen of lateral line mechanosensory hair cells of larval zebrafish, in vivo. PR0T01 exposure provides robust protection of zebrafish hair cells hair cells against a broad range of aminoglycoside antibiotic conditions and exposure levels, and protects rodent inner ear hair cells in vitro and in vivo. The following Specific aims are proposed. 1) Screen analogs of PR0T01 for those hits with optimized protection of hair cells and other drug characteristics using a well characterized, robust and sensitive zebrafish lateral line hair cell assay. 2) Evaluate the most promising new PROTO analogs with secondary assays to determine lead compounds from among promising hits, based on detailed assessment of neomycin-induced hair cell loss, acute and chronic gentamicin-induced hair cell loss, normal efficacy of aminoglycoside as a bacteriostatic agent via MIC/MBL tests, and uptake of the aminoglycoside by hair cells. These experiments will continue to utilize the larval zebrafish hair cell platform. 3) Evaluate lead PROTO analogs for their ability to confer hearing protection against aminoglycoside-induced damage in vivo in mature rats by testing with a well-established auditory brain stem response (AER) assay and by quantitative assessment of inner ear hair cell integrity, 4) Direct IND and phase I clinical preparation of lead compounds in conjunction with NIH supported contractors. The studies outlined in the specific aims will provide a focused analysis of the ability of PR0T01 analogs to protect hair cells from drug-induced damage. Optimization of lead compounds and validation in a mammalian system will provide essential drug development information for future clinical trials in human patients.
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2011 — 2015 |
Raible, David W |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Interdisciplinary Training in Developmental Biology @ University of Washington
DESCRIPTION (Provided by Applicant): This application for continued support of the University of Washington Developmental Biology Training Program will provide support for eleven graduate students for dissertation research in developmental biology. Faculty at the University of Washington and the Fred Hutchinson Cancer Research Center provide an enormous breadth of training opportunities addressing such topics as the origin of cell polarity, germ cell specification and function, body axis formation, stem cell renewal, cell differentiation, cell migration, tissue morphogenesis, metamorphosis, as well as regeneration and death. Trainees are selected from the very competitive graduate programs offered at the University of Washington. They receive in-depth instruction in topics related to developmental biology, responsible conduct of research, and development of skills for a successful career as creative and productive scientists. The program will train future scientists to address topics related to human health, including developmental defects, stem cells, and regenerative medicine. PROJECT NARRATIVE: This application for the Developmental Biology Training Program will provide support for eleven students enrolled in graduate programs at the University of Washington. The program will support dissertation research in modern developmental biology and provide training in the responsible conduct of research. The program will train future scientists to address topics related to human health, including developmental defects, stem cells, and regenerative medicine.
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2013 |
Raible, David W |
R13Activity Code Description: To support recipient sponsored and directed international, national or regional meetings, conferences and workshops. |
2013 Neural Crest & Cranial Placodes Gordon Research Conference @ Gordon Research Conferences
DESCRIPTION (provided by applicant): Neural crest and cranial placodal cells make extensive contributions to embryonic structures, and are of central importance to understanding many congenital disorders. Neural crest-derived cells persist as stem cells into adulthood, and their study has provided broad insights into stem cell biology. They are a highly migratory population of cells during embryogenesis, understanding the regulation of their motility may also shed light on the misregulated invasiveness of metastatic tumor cells. The study of the neural crest and placodes has a rich history, and has been constantly growing, so it is somewhat surprising that to date there has not been a standing meeting dedicated to this topic. This conference will facilitate shared insights and fuel advances in our understanding of two developmentally, evolutionarily, and clinically important populations of cells. The ultimate goal o the conference will be to accelerate the exchange of information across different model systems, and to promote technological innovations and a genome scale understanding of the mechanisms that govern the formation, and subsequent differentiation, of the neural crest and cranial placodes.
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0.906 |
2016 — 2017 |
Raible, David W |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Crispr Screen For Hair Cell Development and Regeneration Regulators @ University of Washington
PROJECT SUMMARY Mechanosensory hair cell loss in the inner ear is a leading cause of hearing and balance disorders. Unfortunately hair cell loss is permanent as humans have little or no capacity for regenerative recovery of hair cells. Although there has been recent progress in the restoration of hair cells in mammals by promoting expression of genes and pathways used during development, functional restoration is largely incomplete and within a limited window of postnatal development. Potential new targets for promoting regeneration, however, are limited. We propose to undertake a high-throughput screen for transcriptional regulators of hair cell development and regeneration in the zebrafish lateral line, a mechanosensory system that is readily accessible to visualization and manipulation in living animals. While there are certainly differences in the organization of the lateral line and inner ear, there is fundamental conservation of many of the genes used in hair cell development and function. The CRISPR system uses easily synthesized guide RNAs to target specific genes and direct Cas9 nuclease to make mutagenic breaks. It is highly efficient, allowing modification of both gene alleles within the same cell and resulting in genetic loss of function. We demonstrate that we can use CRISPR to target expression of genes in the lateral line. We propose a systematic screen for rapid identification of genes that regulate hair cell development and regeneration.
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2017 — 2021 |
Raible, David W |
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. |
Mitochondrial Function and Dysfunction in Hair Cells @ University of Washington
PROJECT SUMMARY Genetic disruptions of over thirty genes affecting mitochondrial functions result in hearing loss. We propose to understand the cellular consequences of representative mutations in mechanosensory hair cells. Our preliminary studies demonstrate that hair cells undergo rapid mitochondrial biogenesis as they mature, and that mitochondria actively respond to mechanosensory cues. We propose studies to understand the regulation of mitochondrial growth and function, focusing on the roles of specialized connections between mitochondria and the endoplasmic reticulum (ER). Growing evidence supports a role for ER-mitochondrial junctions regulating mitochondrial metabolism, dynamics, and stress and for playing a central role in regulated cell death. We propose experiments using live imaging of hair cells in the zebrafish lateral line, a system amenable to study of cellular functions in vivo. We will assess mitochondrial growth, oxidation and ATP utilization in hair cells, and determine the consequences of disrupting ER-mitochondrial communication. We will measure changes in mitochondria in response to mechanical stimuli. Using CRISPR, we will generate zebrafish models of human mitochondrial mutations to assess functional consequences for hair cells. Our experiments will reveal potentially fundamental mechanisms of mitochondria in hair cells and how these mechanisms go awry in human hearing loss.
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2019 — 2020 |
Raible, David W |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Training in Cellular and Molecular Biology @ University of Washington
Abstract The Cellular and Molecular Biology (CMB) training program offers doctoral candidates a broad-based education in molecular and cellular biology at institutions located within the Seattle biomedical corridor. Administered out of the University of Washington (UW), this interdisciplinary program also supports predoctoral trainees at the Fred Hutchinson Cancer Research Center (Fred Hutch) and partner institutions mostly located in the South Lake Union region of the city. The primary objectives of the CMB program are to recruit enthusiastic and motivated students who are passionate about the biomedical sciences and to provide personalized training across a range of disciplines pertaining to basic and translational aspects of molecular and cellular biology. These talented individuals have the opportunity to be mentored by 68 faculty members who are experts in a range of disciplines that include Biochemistry, Biophysical Structure and Design, Immunology, Microbiology, Molecular and Cellular Biology, Neuroscience, Pathology, Pharmacology, and Physiology and Biophysics. CMB trainees enter the program in years 2-4 of graduate school and are selected on academic record and performance in the written and oral components of the annual application competition. Trainees complete mandatory coursework in biostatistics and fundamentals of molecular biology; participate in the Biomedical Research Integrity Lecture series; attend a monthly student organized research conference with speaking and networking opportunities; and take part in the annual CMB Training Grant retreat. Traditionally, the CMB program has successfully partnered with several minority advocacy groups to promote diversity on all campuses. We continue to expand the under-represented minority (URM) footprint and are now emphasizing the recruitment and retention of students who are the first in their families to attend college (first generation) and students with disabilities. This innovative graduate training environment encourages trainees to pursue scientific excellence and endorses peer mentorship and the exploration of alternative career paths. The intended outcome is to nurture a diverse close-knit group of students who are equipped to become the next generation of scientific leaders.
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2021 |
Raible, David W |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Training in Cellular & Molecular Biology @ University of Washington
Abstract The Cellular and Molecular Biology (CMB) training program offers doctoral candidates a multidisciplinary education in molecular and cellular biology at institutions located within the Seattle biomedical corridor. Administered out of the University of Washington (UW), this interdisciplinary program also supports predoctoral trainees at the Fred Hutchinson Cancer Research Center (Fred Hutch) and partner institutions. The primary objectives of the CMB program are to recruit a diverse group of enthusiastic and motivated students who are passionate about the biomedical sciences and to provide personalized training across a range of disciplines pertaining to basic and translational aspects of molecular and cellular biology. These talented individuals have the opportunity to be mentored by 63 faculty members who are experts in a range of disciplines. Students are drawn from seven participating graduate programs that include Biochemistry, Genome Sciences, Immunology, Microbiology, Molecular and Cellular Biology, Neuroscience, and Pharmacology. CMB trainees enter the program in Year 2 of graduate school after holistic selection through written and oral components of the annual application competition. Trainees complete mandatory coursework in biostatistics and fundamentals of molecular biology; participate in the Biomedical Research Integrity Lecture series; attend a monthly student organized research conference with speaking and networking opportunities; receive training in scientific rigor and reproducibility, gain scientific writing skills, participate in a peer mentoring program and take part in the annual CMB Training Grant retreat. Traditionally, the CMB program has successfully partnered with several minority advocacy groups to promote diversity on all campuses. We continue to expand the under-represented minority (URM) footprint and are now additionally emphasizing the recruitment and retention of students who are the first in their families to attend college (first generation) and students with disabilities. This innovative graduate training environment encourages trainees to pursue scientific excellence and endorses peer mentorship and the exploration of alternative career paths. The intended outcome is to nurture a diverse close-knit group of students who are equipped to become the next generation of scientific leaders.
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