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Clifford
F. Weil |
Contact Information:
| Telephone: | 765-496-1917 | Office Location: 2349 Lilly Hall of Life Sciences |
| FAX: | 765-496-2926 | Other Web Sites: |
| Email: | cweil@purdue.edu |
Current Research Interests:
Transposons and DNA repair in maize, Arabidopsis and
yeast
The Genetics of Genetics: genes controlling meiotic recombination in plants
Mutational redesign of maize starch: better health and biofuels
The Maize TILLING Project: reverse genetics for crop functional genomics
Transposons and DNA repair in maize, Arabidopsis and
yeast.
We are interested in better understanding how plants organize, maintain and express their genomes. Our work examines how plant cells repair DNA breaks, a question that also addresses how genes introduced into plants can be targeted to their homologous chromosomal sites and how chromosomes recombine during meiosis. Transgenes generally incorporate at essentially random sites (often in the wrong chromosomal context) through a process of non-homologous DNA end-joining (NHEJ). A homologous recombination mechanism also works at very low levels in plants (though at higher levels in other organisms). We want to know how cells choose one mechanism over the other and how that choice might be manipulated so that maize and other crops can be modified in a more controlled manner.
Our approach has been to study how NHEJ repairs the damage created when Ac/Ds transposons move in maize and Arabidopsis. We have also developed a system in which Ac/Ds transposons are mobile in yeast and other fungi; the damage they cause in yeast is also repaired by NHEJ, and we use yeast NHEJ genes and mutants to better understand the process in plants.
Two key observations drive this research. 1) comparisons among datasets and with those from other plant species show that maize genome rearrangement and DNA repair have features unlike any other eukaryote. Deletion and mutation of bases is less severe in maize than in other species, suggesting maize has evolved more effective DNA repair responses to the presence of the active transposons maintained in its genome by human selection. We are using this difference in a comparative genomics study of NHEJ repair in plants, using Arabidopsis, maize, the maize progenitor teosinte, rice, tomato, barley and other species. We are also examining the effects of DNA repair mutations in our yeast transposition assay system. 2) When an Ac/Ds element excises, the host DNA flanking the transposon forms a DNA hairpin structure, with the backbone of one strand of the double helix covalently bound to the backbone of the complementary strand. This structure is the same one formed when vertebrate immunoglobulin gene segments rearrange to make antibody-encoding genes. Plants do not have homologs of some of the genes essential to this process in vertebrates, yet they repair DNA hairpins very effectively. We want to know what these differences can teach us about how to treat particular forms of immune disease in animals.
The Genetics of Genetics: genes controlling meiotic recombination
Meiotic recombination is another important aspect of DNA breaking and rejoining. In maize, most recombination events (“crossovers”) occur within or very near genes rather than in the repetitive retroelements that comprise 80% of the maize genome. In addition, meiotic crossovers are generally limited to one per chromosome arm through a poorly understood process called crossover interference. An interesting correlation is also that transposons such as Ac/Ds insert preferentially into the same regions where recombination events take place. As part of two collaborative efforts involving six other institutions, we have employed a forward genetic screen to identify over 100 mutants in maize that increase the frequency of recombination events, that decrease recombination, and that reduce crossover interference, a well as a reverse genetic screen to look at mutations in maize and Arabidopsis homologs of known recombination genes. We want to determine whether mutants identified in these screens are global or affect only specific regions of the genome, what effects these mutations have on the number and distribution of the protein machinery that carries out crossover events, (“recombination nodules”), and whether the distribution and frequency of transposon insertion is altered.
Mutational redesign of maize starch: better health and biofuels
We are using a combined genetic, biochemical and protein structural approach to look at how specific mutations in maize alter starch digestibility. Cornstarch that digests more slowly in its cooled form and therefore releases glucose into the bloodstream over a longer period than normal cornstarch can be valuable in combating obesity and diseases related to it, as well as Type II diabetes. Conversely, starch that digests rapidly without the need for cooking can improve the efficiency of producing biofuels such as ethanol and butanol. We have identified ~100 mutant lines that alter starch digestibility, including those that decrease digestibility and those that increase digestibility. We are initiating more detailed characterization of these mutations and, in collaboration with the Whistler Center for Carbohydrate Research (located at Purdue), characterizing what they do to starch fine structure, to the interaction of starch with other cellular components and to the ultrastructure and development of the starch granule. Additional biofuels projects include modifying maize kernel architecture and developing maize lines that accumulate sugars in the stalk.
The Maize TILLING Project (http://genome.purdue.edu/maizetilling/)
One of the most powerful tools available for understanding gene function is to analyze the effects of mutating that gene. We operate the Maize TILLING Project, an NSF-supported resource, as a service to the international maize community. TILLING is a technology, originally developed for Arabidopsis, that allows us to screen through the DNAs of a large, EMS mutagenized population of maize and quickly identify any individuals in that population that have a mutation in a user’s gene of interest. We then sequence the mutations we find and return this information, the predicted effects of the mutations and, most importantly, seed carrying the mutations to the person who initiated the request. These mutants can then be analyzed further to better understand gene function. We are developing projects that apply this technique to other crops as well, including soybean, sorghum, marigold, switchgrass and ryegrass, and welcome inquiries into its application to other crops.
Member of:
Purdue Division of Genetics
Purdue Plant Biology Program,
PULSe Chromatin and Gene Expression Training
Group,
PULSe Plant Biology Training Group
Recent Publications:
Weil, C. F. and R. Kunze (2000). Transposition of maize Ac/Ds transposable elements in the yeast Saccharomyces cerevisiae. Nature Genet. 26: 187-190.
Giedt, C.D. and C.F. Weil (2000) Developmental control of Ac/Ds transposition by the LAG1-O mutation in maize. Plant J. 24:815
Kunze, R and C.F. Weil. (2002) The hAT and CACTA superfamilies of plant transposons. In Mobile DNA II, N. Craig, R. Craigie, M. Gellert and A. Lambowitz eds., ASM Press, Washington, DC, pp.565-610
Yu, J.-H., K. Marshall, M. Yamaguchi, J.E. Haber and C.F. Weil. (2004) Microhomology-dependent end-joining and repair of transposon-induced DNA hairpins by host factors in yeast. Molec. Cell. Biol. 24:1351
Weil, C. F., R. Monde, B. Till, L. Comai and S. Henikoff (2005) Mutagenesis and functional genomics in maize. Maydica 50:415-424
Yang, G., C. F. Weil and S. R. Wessler (2006) A rice Tc1/mariner-like element transposes in yeast. Plant Cell 18:2469-2478
Weil, C. F. and R. Monde (2006) Getting the point—mutations in maize. Plant Genome (in press).
Groth, D., R. Helms, B. Hamaker, L. Mauer and C. Weil. A high-throughput assay reveals mutants that alter digestion rates of corn starch, (submitted to Starch)
Waterworth, W., Ç. Altun. K. Young, S. Armstrong, C. Weil, C. Bray, C. West (2006) A plant homolog for Nbs1, the signaling component of the Mre11 DNA repair/recombination complex, (submitted to PNAS)
Courses:
Undergraduate Introductory Genetics (AGRY 320)
Graduate Advanced Plant Genetics (AGRY 530)
Graduate Genomics (AGRY 600/BIOL 595W)
Positions Held:
Associate Professor, Dept. of Agronomy, Purdue University, 2001-present
Associate Professor, Dept. of Biological Sciences, University of Idaho,
1998-2001
Assistant Professor, Dept. of Biological Sciences, University of Idaho,
1992-1998
Postdoctoral Research Associate, University of Georgia, 1988-1992
Postdoctoral Research Associate, Ohio State University, 1984-1988
Awards and Honors:
NIH Predoctoral Training Grant, 1982-1984
U. Idaho Alumni Award for Teaching Excellence, 1998 (student nominated)
Purdue Seeds of Success Research Award, 2004
Elected Fellow, American Association for the Advancement of Science, 2006
Education:
B.S., University of California-Davis, 1978
Ph.D., Cornell University, 1984
Date joined staff: 2001
Last updated: October, 2007