1995 — 2001 |
Goodwin, Elizabeth B. |
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. |
3 Utr Control of Tra-2 Translation in C Elegans @ Northwestern University
How are some genes that specify cell fates translationally regulated so that cells are determined at the right time and place? We propose to study this fundamental question of developmental gene regulation by analyzing the translational regulation of the C. elegan sex determination gene, tra-2. We have shown that a direct repeat, located in the 3' untranslated region (3'UTR), is necessary for repressing the translation of tra-2 mRNA. This repression is required for the proper specification of sexual fates. We have identified an RNA binding factor that binds to the direct repeat. We have also identified a gene, laf-1, that may be involved in this regulation; mutations in laf-1 disrupt the transitional control of reporter constructs by the 3'UTR. During the next five years, we propose to investigate the mechanism by which the 3'UTR controls translation of tra-2 mRNA during development. First, using reporter constructs, we will delineate the necessary cis- acting sequences required for the 3'UTR regulation. In addition, we will ask if the position or orientation of these sequences is important for control. We will study whether the direct repeat controls translation by regulating the length of the poly(A) tail. Second, using RNA gel retardation analysis and reporter constructs, we will investigate whether the binding factor may be a translational inhibitor by correlating the ability of the factor to bind mutant 3'UTRs with the capability of these 3'UTRs to regulate translation. Third, we will genetically characterize the known laf-1 alleles and determine the laf-1 loss-of-function phenotype. This analysis will elucidate the role of laf-1 in the 3'UTR control, and is necessary for the cloning of the gene. Fourth, we will clone laf-1, which will give further insight into its part in the 3'UTR control, and give us the tools to analyze the 3'UTR regulation, biochemically. Fifth, using genetics, reporter constructs, and TRA-2 antibodies, we will study how the 3'UTR regulation changes during development, and identify genes that may control these changes. The health relatedness of this work derives from its contribution to an understanding of fundamental control of gene activity by translational regulation. This class of post-transcriptional regulation is being found to be common in many metazoans, including man.
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0.958 |
2004 — 2005 |
Chisholm, Andrew Niswander, Lee (co-PI) [⬀] Goodwin, Elizabeth |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Santa Cruz Meeting On Developmental Biology; August 5-9, 2004; Santa Cruz, Ca @ University of California-Santa Cruz
Funding is requested for the 2004 Santa Cruz meeting on Developmental Biology, to be held 5-9 August 2004 at the University of California, Santa Cruz, California. Previous Santa Cruz Developmental Biology (SCDB) meetings have provided a stimulating and focused forum for discussion of current research by developmental biologists. SCDB meetings are international in scope and are accessible to junior faculty, postdoctoral fellows, and graduate students. SCDB meetings emphasize the conceptual unity of developmental biology at the level of mechanism, while covering and eclectic range of current topics. The topics for the 2004 meeting include: pattern formation; morphogenesis and cell migration; evolution and development; stem cells; non-coding RNAs; cellular asymmetry; organogenesis; development of the nervous system, and disease. Speakers are invited from both plant and animal development fields. The 2004 meeting will have 40-50 platform speakers, of which 10-15 will be chosen from abstracts submitted to the meeting organizers. Platform sessions are organized to allow ample time for discussions; the extensive discussion periods have been cited as one of the best features of previous SCDB meetings. Posters are continuously displayed and several poster sessions are scheduled in the meeting, as well as time for informal discussions.
The 2004 SCDB meeting will build on the success of previous meetings in this series. SCDB meetings are hosted by the University of California, Santa Cruz (UCSC). The conference site is arranged so that platform sessions, posters, accommodation, and dining facilities are in close proximity; access for disabled participants is ensured by UCSC. The UCSC setting is cost effective. Conference logistics are provided by UCSC Conference Services. The UCSC campus is within an hour's drive of the San Francisco Bay Area; travel from nearby airports is simple, but the site is sufficiently isolated and pleasant that speakers and participants tend to stay in residence for the entire meeting. Thus, the SCDB meeting, although modeled on a Gordon Research Conference, has several additional advantages that have made it a valued venue for the Developmental Biology community.
Intellectual merit: The Santa Cruz meetings on Developmental Biology have become a well established venue for presentation and discussion of current results across the field of developmental biology. Unlike other comparably sized meetings, SCDB meetings emphasize interdisciplinary approaches, and are not focused on specific processes or organisms. One theme of the 2004 meeting will be the use of comparative and evolutionary approaches to understanding development; for example, in addition to classical model systems, the meeting will include presentations on mollusks, planarians, and stickleback fish. The SCDB meeting will emphasize the general implications of such studies for developmental mechanisms.
Broader impact: The broader impacts of the 2004 SCDB meeting will be in fostering developmental biology research and in training. Previous SCDB meetings have stimulated collaborative research by bringing together an eclectic group of active investigators in a collegial setting. It is anticipated that the 2004 meeting will likewise foster new collaborations.
Previous SCDB meetings have also had broader impact in enhancing the training of graduate students, postdoctoral fellows, and junior faculty in the field of developmental biology. The size and organization of SCDB meetings allows all attendees to present their research and to fully participate in discussions. SCDB meeting attendees also regularly include representatives from major scientific journals. Active participation in meetings and exposure to prominent scientists in the field are both important training goals for scientists in the early stages of their careers.
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0.942 |