Gregory P. Copenhaver - US grants

This project will support the 14th International Conference on Arabidopsis Research, which will be held at the University of Wisconsin, Madison on June 20-24, 2003. The aim is to provide an opportunity for the exchange of ideas among researchers of the international Arabidopsis community. The conference will include sessions on genetics, genomics, metabolism, metabolic regulation, cell biology, inductive processes, genetic mechanisms, evolution, pattern formation, cell fate, reproduction, and responses to the biotic and aboitic environment. An important component of the conference is the presentation of current research by approximately 42 speakers. Graduate students, postdoctoral researchers or junior faculty will present the majority of these talks. This will ensure presentation of the latest results, promote education of students and postdoctoral fellows and provide important career development for the selected speakers. This project will primarily support attendance of young scientists and of researchers from minority-serving institutions.

Meiosis, the reductive division of the genome in preparation for fertilization, is a critical phase in the life-cycle of sexually reproducing organisms. During meiosis homologous chromosomes interact resulting in the heritable rearrangement of DNA, through reciprocal exchange between homologous chromosomes (crossing over, CO) or gene conversion (GC). In most eukaryotes these events ensure proper chromosome segregation, facilitate DNA repair and provide a basis for genetic diversity. Detailed models describing recombination mechanisms have been proposed and measurements of the frequency, and distribution of GC events can be used to test the accuracy of these models. Meiotic recombination also causes the breakdown linkage disequilibrium (LD), the non-random association of sets of alleles at linked loci, over evolutionary time which population geneticists use to better understand how species, their phenotypes, and their genomes evolve. Recent models suggest that GC may be as important as CO in breaking down LD in some genomic regions. The immediate goals of this project are to measure GC frequency at multiple loci in two distinct organisms, the plant Arabidopsis thaliana and the metazoan Drosophila melanogaster. The investigators will also make population genetic estimates of recombination at the same loci and compare these estimates with direct measurements of GC and CO in order to refine population genetic models of recombination and its effect on genome wide patterns of LD.
The long-term goal of the project is to understand how meiotic recombination operates in multi-cellular organisms and how it influences genome variation and evolution. In addition to deepening our understanding of a classic genetic problem - gene conversion - this proposal also provides broader impact by building truly interdisciplinary collegial partnerships, creating a platform for participation by junior scientists from underrepresented groups and emphasizing graduate level education in the form of first-hand research and collaboration.

A grant has been awarded to The University of North Carolina at Chapel Hill (UNC) under the supervision of Dr. Alan M. Jones entitled "Rapid Image Acquisition of Dynamic Arabidopsis Cells and For High-throughput Genetic Screens" for the purpose of acquiring and maintaining a specialized microscope. The enormous progress made in the plant sciences from sequencing the Arabidopsis genome has propelled research to the next higher research plane, where examining how and when cellular proteins interact over time at a high spatial resolution has become the new standard in demand. Both the demand and the need for sophisticated imaging instrumentation have increased, pari passu. However, imaging fluorescently-tagged proteins in plant cells faces several surmountable challenges. One is the dynamic nature of plant cells due to cytoplasmic streaming (rapid cellular movement) that occurs with speeds greater than the speed of standard capture by a standard confocal microscope (which is a specialized microscope that enables one to visualize fluorescently-modified proteins in all kinds of live cells). Therefore, to capture transient protein-protein interactions within plant cells requires a specialized confocal microscope that enables rapid acquisitions nearly simultaneously through the cell, over a short time scale. Reconstitution of this data will be used to produce a 3-dimensional view of plant protein-protein interactions in vivo over time. This grant will enable 8 highly-productive plant scientists at UNC to make significant and faster contributions to fundamental science leading to increased crop production, plant disease resistance, and biofuels production.

The broader impact will occur in the classroom, in public, and in the research labs. The use of a confocal microscope will be introduced to upperclassmen in an intense, hands-on cell biology laboratory. The public will become aware of the power of rapid imaging through an educational display and presentations by the PIs. The plant science group at UNC collectively trains 20 undergraduates, 15 predoctoral, and 30 postdoctoral students each year. The requested instrument will also serve the confocal imaging needs of many additional labs on campus. It is the first of its kind on the UNC campus and only the second like it in the state of North Carolina. Many scientists beyond the plant science group will greatly benefit from this specialized microscope.

Intellectual Merit: Meiosis, the reductive division of the genome in preparation for fertilization, is a critical biological process. During meiosis, homologous chromosomes interact resulting in the heritable rearrangement of DNA through reciprocal exchange between homologous chromosomes by processes referred-to as crossing over and gene conversion. In most eukaryotes, these events ensure proper chromosome segregation, facilitate DNA repair, and provide a basis for genetic diversity. Molecular geneticists have made substantial progress in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals. As a result, detailed models describing recombination mechanisms have been proposed. In most organisms, a key protein in these mechanisms is DMC1, which mediates the establishment of physical linkages between homologous chromosomes during recombination. Intense focus on DMC1 in several model organisms has revealed that its activity is closely regulated by a host of mediator proteins. While DMC1 or similar proteins (RecA homologs) are found in organisms as diverse as bacteria, fungi, plants and animals, their mediators are not as well conserved. Indeed, the model plant Arabidopsis thaliana shares only four of the ten proteins proposed to regulated DMC1 in the budding yeast Saccharomyces cerevisiae. As a prelude to this project, ten mutants (suppressors) have been identified that may interact with Arabidopsis DMC1. Understanding the proteins that interact with DMC1 (identified as suppressors of dmc1 mutants) will enable the description of the mechanisms that plants use to mediate meiotic recombination. In addition, expanding our understanding of plant meiotic recombination has the potential for advancing plant biotechnology including our ability to engineer plant genomes by harnessing recombination.

Broader Impacts: The project will create opportunities for participation in cutting-edge research by young scientists from under-served communities. In addition, the PI will continue to participate in and develop a class for advanced undergraduates, graduates, and postdocs that focuses specifically on meiosis and recombination - this class was initiated as part of the broader impact efforts from a prior NSF award.

DESCRIPTION (provided by applicant): Partial support is requested for an international meeting on Meiosis as part of the Gordon Research Conferences (GRC) to be held at Colby-Sawyer College in New London, NH on June 1-6, 2014. In addition, support is requested for the Meiosis Gordon Research Seminar (GRS) that will be held in the same location, immediately prior to the GRC (May 31 - June 1, 2014). The GRS is a 1.5 day meeting, organized by graduate students and postdoctoral fellows, which offers an opportunity for junior researchers to network and discuss the topics that will be covered in more depth during the 41/2-day Meiosis GRC. The long term goal of the conferences is to understand the fundamental mechanisms that ensure the stabile inheritance of the genome during meiotic cell divisions in both normal and disease conditions. The specific aims of the meeting are to: foster innovation, create networks between young and established investigators, rapidly disseminate new and unpublished results, and promote interdisciplinary synergies. The GRC will gather approximately 175 participants, including 53 speakers, to present and discuss cutting-edge, mostly unpublished research. The program comprises 9 plenary sessions that broadly address current issues in meiotic recombination, meiotic progression and cell cycle checkpoints, epigenetic control of meiotic processes, regulation of meiotic gene expression, chromosome pairing and synapsis, sister chromatid cohesion, chromosome interactions with the nuclear envelope, chromosome segregation, and the evolution and natural variation of meiotic processes. Four poster sessions, open to all participants throughout the conference will provide a basis for extended and in- depth critical discussions. The poster sessions are a particularly valuable forum for forging interdisciplinary collaborations and for new investigators to join networks. The GRS will include between 50-60 participants and will have three plenary and one poster session. This application has direct relevance to human health. Roughly 58% of human conceptions suffer an error in meiosis that results in miscarriage or birth defects related to chromosomal abnormalities. In addition, many of the mechanisms that repair programmed double strand breaks during meiosis also serve to protect mitotically dividing cells from harmful DNA lesions. Therefore, understanding meiosis provides novel insights into genome stability and preventing cancer. This pair of conferences brings together graduate students, postdocs, young investigators and established PIs to push the leading edge of innovation and knowledge in this critical area of reproductive health.