Bryn Mawr College
Park Science Building, room 222
Department of Biology
Bryn Mawr College
101 N. Merion Avenue
Bryn Mawr, PA 19010-2899
Biology 110 is an introductory-level course, designed to encourage students to explore the field of biology at multiple levels of organization: molecular, cellular, organismal and ecological; Biology 111 will explore these areas of biology through a unifying theme. This year Biology B110-002 will investigate the relationship between genotype and phenotype through analysis of inheritance patterns in families and populations, examination of the regulation and decoding of genetic information that ultimately produces whose structure/function dictates cellular activity, and analysis of how mutations affect developmental processes. We will also discuss ethical issues associated with genetic testing. Lecture three hours, laboratory three hours a week. There are no prerequisites for this course.
Biology 201 - Genetics
An introduction to heredity and variation, focusing on topics such as classical Mendelian genetics, linkage and recombination, chromosome abnormalities, population genetics and molecular genetics. Examples of genetic analyses are drawn from a variety of organisms, including bacteria, viruses, Drosophilaand humans. Lecture three hours a week. Prerequisites: Biology 110-111 and Chemistry 103-104.
Biology 376 - Integrated Biochemistry and Molecular Biology II
This course is the second semester of Integrated Biochemistry and Molecular Biology. Students will continue investigating macromolecules, molecular pathways and gene regulation through lecture, critical reading and discussion of primary literature and laboratory experimentation. Three hours of lecture, three hours of laboratory per week. Prerequisites: Biology 201 - Genetics, Biology 375 - Integrated Biochemistry and Molecular Biology I, or permission of instructor.
Biology 393 - Senior Seminar in Molecular Genetics (not offered 2013-2014)
This course focuses on topics of current interest and significance in molecular genetics, such as chromatin structure and mechanisms of gene regulation. Students critically read, present and discuss in detail primary literature relevant to the selected topic. In addition, students write, defend, and publicly present one long research paper or thesis. Three hours of class lecture and discussion per week, supplemented by frequent meetings with individual students. Prerequisites: Biology 201, Biology 376 or permission of instructor.
Biology 399 - Senior Seminar in Laboratory Investigations
This seminar provides students with a collaborative forum to facilitate the exchange of ideas and broaden their perspective and understanding of research approaches used in various sub-disciplines of biology. There will be a focus on the presentation, interpretation and discussion of data, and communication of scientific findings to diverse audiences. In addition, students write, defend and publicly present a paper on their supervised research project. Three hours of class discussion each week. Co-requisite: enrollment in BIOL403.
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My lab focuses on understanding the mechanism of genomic imprinting. Genomic imprinting is a mammalian-specific phenomenon whereby the expression of a subset of genes depends on their parental origin. In other words, although we inherit one copy of every gene from our mothers and one copy from our fathers, there are a small number of genes for which only the maternally inherited copy is expressed and a small number for which only the paternally inherited copy is expressesd. There are two major consequences of this unusual form of gene regulation. First, mutations in imprinted genes act in a dominant fashion since there is not a second copy whose wild-type expression can compensate for the mutation. Second, every mammal needs to have a genetic contribution from both a male and a female parent - otherwise, genes critical for normal development will not be expressed. Failure to achieve genomic imprinting can result in developmental disorders such as Beckwith-Wiedemann, Prader-Willi and Angelman syndromes.
One main question in the field of genomic imprinting is: how can the cellular machinery distinguish the maternally inherited allele from the paternally inherited allele so that it knows which copy should be expressed and which copy should remain silent? The simple answer is that the maternal and paternal alleles must be marked so that they appear to be different from each other. To date, the best candidate for the imprinting mark is DNA methylation. In mammals, DNA methylation is a modification of cytosines that are present in CG pairs, such that the cytosines have a methyl group covalently attached at the 5' position. This type of modification is called epigenetic because it is a modification of the DNA structure but does not alter the DNA sequence. The reason DNA methylation stands out as a candidate for the imprinting mark is that most imprinted genes are associated with a region of differential methylation - for example, the silent paternal allele is methylated while the expressed maternal allele is unmethylated.
As mentioned above, all imprinted genes are associated with a region of differential methylation which serves as an imprinting control region. However, the precise regulation of imprinted genes requires additional epigenetic modifications, including secondary differentially methylated regions (DMRs) and differential distribution of modified histones on the parental alleles, or copies, of imprinted genes. Secondary DMRs are regions at which differential methylation is not inherited via the gamete; rather, allele-specific methylation at secondary DMRs is acquired post-fertilization. One aspect of my research is focused on understanding when methylation is acquired during embryogenesis. To do this, my lab conducts analysis of methylation patterns at imprinted genes during various stages of development in the mouse. Thus far, we have analyzed the acquisition of methylation at secondary DMRs associated with the imprinted genes Cdkn1c and Gtl2. We have learned that these two genes acquire methylation on their paternal alleles at different developmental stages, indicating that there is not a single developmental stage during which allele-specific methylation is established.
While it is clear that DNA methylation plays a role in regulating the expression of imprinted genes, it is also clear that differential DNA methylation cannot be the only factor distinguishing the maternal and paternal alleles from each other. Rasgrf1 is an imprinted gene at which the paternal allele is marked with DNA methylation. However, the DNA methylation pattern at Rasgrf1 does not directly correlate with its expression pattern. Rasgrf1 is an example of a tissue-specific imprinted gene: it is expressed solely from the paternally inherited copy in some tissues, such as brain, but is expressed from both the paternal and the maternal copy in other tissues, such as lung. Therefore, there must be other factors responsible for regulating the tissue-specific imprinting of this gene. Histone modification is one candidate that may be playing a role in the complex regulation of Rasgrf1. Histones are proteins that DNA wraps around in order to achieve the first level of chromosome compaction. The addition of different chemical groups, such as methyl and acetyl groups, to histone proteins affects the structure of the chromatin and the degree of DNA compaction. My lab is currently investigating the distribution of modified histones on the parental alleles of Rasgrf1in order to determine if they play a role in achieving imprinting at this gene.
There are opportunities for student research in my lab during the course of the academic year as well as in the summer.
Students conducting research with me include:
Paige De Rosa, class of 2014
Aimee Heerd, class of 2014
Rachel Shields, class of 2015
Katia Vlasova, class of 2015
image at right: Jessica, Rachel, Paige, Katia & Aimee
Former research students include:
Anna Arnaudo, class of 2002
Emily Bergbower, class of 2011
Alison Best, class of 2003
Alyson Dymkowski, class of 2004
Sara Fielder, class of 2013
Alyssa Gagne, class of 2011
Jennifer Gerfen, class of 2006
Christina Harview, class of 2009
Lu Mei He, class of 2006
Abby Hochman, class of 2013
Rebecca Joseph, class of 2013
Kirsten Jusewicz-Haidle, class of 2009
Nelly Khaselev, class of 2011
Francesca Marangell, class of 2009
Sadie Marlow, class of 2011
Sarah McCawley, class of 2002
Kayla McDaniel, class of 2012
Lauren McNelly, class of 2012
Snehal Naik, class of 2003
Anuja Ogirala, class of 2001
Yaena Park, class of 2008
Stephanie Pollack, class of 2008
Charlotte Rahn-Lee, class of 2005
Amelie Raz, class of 2011
Sarah Schnellbacher, class of 2013
Geneva Stein, class of 2006
Celia Tong, Haverford College class of 2013
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Nowak, K., Stein, G., Powell, E., He, L.M., Naik, S., Morris, J., Marlow, S. and T.L. Davis, 2011, Establishment of paternal allele-specific DNA methylation at the imprinted mouse Gtl2 locus, Epigenetics 6(8): 1012-1020.
Dockery, L., J. Gerfen, C. Harview, C. Rahn-Lee, R. Horton, Y. Park and T.L. Davis, 2009, Differential methylation persists at the mouse Rasgrf1 DMR in tissues displaying monoallelic and biallelic expression, Epigenetics 4(4): 241-247.
Bhogal, B., A. Arnaudo, A. Dymkowski, A. Best and T.L. Davis, 2004,
Methylation at mouse Cdkn1c
is acquired during post-implantation development and functions to
maintain imprinted expression, Genomics
Davis, T.L., G.J. Yang, J. McCarrey and M.S. Bartolomei, 2000, The H19 methylation imprint is erased and reestablished differentially on the parental alleles during male germ cell development, Human Molecular Genetics 9(19): 2885-2894.
Dawes, H.E., D.S. Berlin, D.M. Lapidus, C. Nusbaum, T.L. Davis and B.J. Meyer, 1999, SDC-2 triggers hermaphrodite sexual development and targets nematode dosage compensation machinery to X chromosomes, Science 284(5421): 1800-1804.
Davis, T.L., J.M. Trasler, S.B. Moss, G.J. Yang and M.S. Bartolomei, 1999, Acquisition of the H19 methylation imprint occurs differentially on the parental alleles during spermatogenesis, Genomics 58(1): 18-28.
Davis, T.L., K.D. Tremblay and M.S. Bartolomei, 1998, Imprinted expression and methylation of the mouse H19 gene are conserved in extraembryonic lineages, Developmental Genetics 23(2): 111-118.
Davis, T.L. and B.J. Meyer, 1997, SDC-3 coordinates the assembly of a dosage compensation complex on the nematode X chromosome, Development 124(5): 1019-1031.
Davis, T.L., D.R. Helinski, and R.C. Roberts, 1992, Transcription and autoregulation of the stabilizing functions of broad-host-range plasmid RK2 in Escherichia coli, Agrobacterium tumefaciens and Pseudomonas aeruginosa, Molecular Microbiology 6(14): 1981-1994.
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The following abstract will be presented at the 2012 Mid-Atlantic Society for Developmental Biology Regional Meeting, May 11-12, 2012.
Analysis of epigenetic modifications at the imprinted Rasgrf1 locus in mouse
Lauren McNelly ('12), Sara Fielder ('13) and Tamara L. Davis
Department of Biology, Bryn Mawr College, Bryn Mawr, PA 19010-2899 USA
Genomic imprinting is a form of transcriptional regulation whereby a subset of genes is expressed from only one of the two parental alleles. The regulation of imprinted genes is complex and is influenced by epigenetic modifications such as DNA methylation, histone methylation and histone acetylation. The differential distribution of these epigenetic modifications on the parental alleles has been shown to play a role in implementing the parent of origin-specific expression pattern observed at imprinted genes. We are interested in better understanding the mechanisms responsible for achieving tissue-specific imprinting, and have focused our studies on Rasgrf1 in mouse. Rasgrf1 encodes a guanine nucleotide exchange factor that is expressed at high levels in the central nervous system and plays a role in learning and memory. Paternal allele-specific expression of Rasgrf1 is detected in brain, liver and placenta, while lung, thymus, kidney and stomach exhibit biallelic expression. DNA methylation of the paternally inherited imprinting control region is required for expression of the paternal Rasgrf1 allele in brain. However, the imprinting control region is also methylated solely on the paternal allele in tissues exhibiting biallelic expression of Rasgrf1, suggesting that other factors are involved in controlling the tissue-specific imprinting of this gene. We are currently investigating the role histone modifications play in differentiating between the maternal and paternal Rasgrf1 alleles and regulating their expression by comparing the distribution of modified histones in brain and liver chromatin, where Rasgrf1 expression is imprinted, to their distribution in lung and kidney chromatin, where Rasgrf1 expression is biallelic. Thus far, we have examined the allelic distribution of five different histone modifications at both the Rasgrf1 imprinting control region and the promoter in neonatal brain, liver and kidney-derived chromatin. Our preliminary data suggest that modifications associated with permissive chromatin states, such as acetylated histone H3, are generally associated with the unmethylated maternally-derived ICR and the promoter of the expressed paternal allele in tissues exhibiting monoallelic expression of Rasgrf1, while repressive modifications such as trimethylated histone H3K9 are generally associated with the methylated paternally-derived ICR and the promoter of the silent maternal allele. Our analyses of modified histone distribution in tissues exhibiting biallelic expression of Rasgrf1 are underway. This poster will describe our recent results and current directions.
The following abstract will be presented at the 45th Annual Meeting of theSociety for the Study of Reproduction, August 12-15, 2012.
Comparative analysis of DNA methylation acquisition at the imprinted Gtl2/Dlk1 locus during mouse embryonic development
Alyssa Gagne ('11), Mahvish Qureshi ('10), Kayla McDaniel ('12), Jeanette Bates ('12) and Tamara L. Davis
Department of Biology, Bryn Mawr College, Bryn Mawr, PA 19010-2899 USA
Genomic imprinting results in parent of origin-specific monoallelic expression of a subset of mammalian genes. Research has shown that parent of origin-specific differences in DNA methylation are inherited via the gametes at fertilization, and function to mark parental origin and modulate the expression of imprinted genes. Less is known about the further refinement of chromatin structure that is achieved during post-fertilization development via histone modification and additional DNA methylation; these epigenetic changes are hypothesized to play a role in maintaining imprinted expression as well as establishing modifications necessary for tissue-specific imprinting. The mouse Dlk1/Gtl2 locus contains three distinct paternally methylated differentially methylated regions (DMRs). The IG-DMR functions as the imprinting control region, and paternal allele-specific methylation is inherited via the sperm. In contrast, paternal allele-specific DNA methylation is acquired at the Gtl2-DMR and Dlk1-DMR during post-fertilization development. To test the hypothesis that post-fertilization epigenetic modifications are coordinately controlled across the 100 kb Dlk1/Gtl2 imprinting cluster, we are currently examining the temporal acquisition of paternal allele-specific DNA methylation at the mouse Dlk1 gene during post-implantation development. A preliminary analysis of DNA methylation profiles at the Dlk1- and Gtl2-DMRs during embryonic development suggests that the timing of these events is not coordinately regulated. This poster will describe our recent results and current directions.
The following is the abstract from
a paper published in Epigenetics 6(8): 1012-1020.
Establishment of paternal allele-specific DNA methylation at the imprinted mouse Gtl2 locus.
Kamila Nowak ('08), Geneva Stein ('06), Elizabeth Powell ('05), Lu Mei He ('06), Snehal Naik ('03), Jane Morris ('10), Sara Marlow ('11) and Tamara L. Davis
The monoallelic expression of imprinted genes is controlled by epigenetic factors including DNA methylation and histone modifications. In mouse, the imprinted gene Gtl2 is associated with two differentially methylated regions: the IG-DMR, which serves as a gametic imprinting mark at which paternal allele-specific DNA methylation is inherited from sperm, and the Gtl2-DMR, which acquires DNA methylation on the paternal allele after fertilization. The timeframe during which DNA methylation is acquired at secondary DMRs during post-fertilization development and the relationship between secondary DMRs and imprinted expression have not been well established. In order to better understand the role of secondary DMRs in imprinting, we examined the methylation status of the Gtl2-DMR in pre- and post-implantation embryos. Paternal allele-specific DNA methylation of this region correlates with imprinted expression of Gtl2 during post-implantation development but is not required to implement imprinted expression during pre-implantation development, suggesting that this secondary DMR may play a role in maintaining imprinted expression. Furthermore, our developmental profile of DNA methylation patterns at the Cdkn1c- and Gtl2-DMRs illustrates that the temporal acquisition of DNA methylation at imprinted genes during post-fertilization development is not universally controlled.
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