Dr. Tamara L. Davis
Professor and Chair of Biology

 


Education
B.A. University of California at San Diego, 1991
Ph.D. University of California at Berkeley, 1996
Postdoctorate University of Pennsylvania

Contact information
Bryn Mawr College
Park Science Building, room 222
phone: 610-526-5065
fax: 610-526-5086
tdavis@brynmawr.edu

mailing address:
Department of Biology
Bryn Mawr College
101 N. Merion Avenue
Bryn Mawr, PA 19010-2899

 


Courses

Biology 110 - Biological Exploration I: Genetic Control of Phenotype

 

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 proteins whose structure/function dictates cellular activity, and analyses of mutations and how they 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 or Biology 375 - Integrated Biochemistry and Molecular Biology I or permission of instructor.

Biology 393 - Senior Seminar in Molecular Genetics (not offered 2014-2015)

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 (taught every spring by various members of the Biology Department)

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.

Go to the Bryn Mawr College Biology Department Homepage
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Research Interests

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, parent of origin-specific 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 does 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 dinucleotides, 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 of an imprinted gene may be methylated while the expressed maternal allele is unmethylated.

As mentioned above, all imprinted genes are associated with a primary region of differential DNA 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, and how these secondary DMRs differ from primary imprinting control regions. To do this, my lab conducts analysis of DNA methylation patterns at imprinted genes during various stages of development in the mouse. Thus far, we have analyzed the acquisition of DNA methylation at secondary DMRs associated with the imprinted genes Cdkn1c, Gtl2 and Dlk1. We have learned that Cdkn1c acquires DNA methylation on its paternal allele at a different developmental stage than Gtl2 and Dlk1, and that the DNA methylation pattern at Dlk1 continues to change during development. These results indicate that there is not a single developmental stage during which allele-specific methylation is established. More recently, we observed that the DNA methylation has an unexpected high level of asymmetry on the complementary strands of the Dlk1 gene. We are currently conducting experiments to determine if this asymmetry is unique to Dlk1 or whether it is a common feature of secondary DMRs, and to determine the biochemical basis for this asymmetry.

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 both imprinted and non-imprinted tissues in 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:
Carolyne Face, class of 2015

Nicole Hamagami, class of 2016

Rachel Shields, class of 2015

Kristian Sumner, class of 2017

Katia Vlasova, class of 2015

image at right: 2014-2015 research team -

Nicole, Rachel, Katia & Carolyne

Former research students include:

Jessica Arbon, class of 2014

Anna Arnaudo, class of 2002
Jeanette Bates, class of 2012

Emily Bergbower, class of 2011

Alison Best, class of 2003
Balpreet Bhogal, class of 2004
Meredith Calandra, class of 2004
Amber Carmo, class of 2001

Paige De Rosa, class of 2014
Lauren Dockery, class of 2008

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

Aimee Heerd, class of 2014

Abby Hochman, class of 2013
Rachel Horton, class of 2007

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
Avery Miller, class of 2005
Jane Morris, class of 2010

Snehal Naik, class of 2003
Kamila Nowak, class of 2008

Anuja Ogirala, class of 2001
Tammy Owens, class of 2002

Yaena Park, class of 2008

Stephanie Pollack, class of 2008
Liz Powell, class of 2005
Mahvish Qureshi, class of 2010

Charlotte Rahn-Lee, class of 2005
Lilah Rahn-Lee, class of 2005

Amelie Raz, class of 2011

Sarah Schnellbacher, class of 2013
Meghan Shayhorn, class of 2001

Geneva Stein, class of 2006

Celia Tong, Haverford College class of 2013
Ruthie Worrell, class of 2001

 

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Publications

Gagne, A., Hochman, A., Qureshi, M., Tong, C., Arbon, J., McDaniel, K. and T.L. Davis, 2014, Analysis of DNA methylation acquisition at the imprinted Dlk1 locus reveals asymmetry at CpG dyads, Epigenetics & Chromatin 2014 7:9.

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 84(6): 961-970.

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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Current Abstracts

The following is the abstract from a paper recently published in Epigenetics & Chromatin 2014 7:9.

Analysis of DNA methylation acquisition at the imprinted Dlk1 locus reveals asymmetry at CpG dyads.
Alyssa Gagne ('11), Abigail Hochman ('13), Mahvish Qureshi ('10), Celia Tong ('13), Jessica Arbon ('14), Kayla McDaniel ('12) and Tamara L. Davis


Background: Differential distribution of DNA methylation on the parental alleles of imprinted genes distinguishes the alleles from each other and dictates their parent of origin-specific expression patterns. While differential DNA methylation at primary imprinting control regions is inherited via the gametes, additional allele-specific DNA methylation is acquired at secondary sites during embryonic development and plays a role in the maintenance of genomic imprinting. The precise mechanisms by which this somatic DNA methylation is established at secondary sites are not well defined and may vary as methylation acquisition at these sites occurs at different times for genes in different imprinting clusters. Results: In this study, we show that there is also variability in the timing of somatic DNA methylation acquisition at multiple sites within a single imprinting cluster. Paternal allele-specific DNA methylation is initially acquired at similar stages of post-implantation development at the linked Dlk1 and Gtl2 differentially methylated regions (DMRs). In contrast, unlike the Gtl2-DMR, the maternal Dlk1-DMR acquires DNA methylation in adult tissues. Conclusions: These data suggest that the acquisition of DNA methylation across the Dlk1/Gtl2 imprinting cluster is variable. We further found that the Dlk1 differentially methylated region displays low DNA methylation fidelity, as evidenced by the presence of hemimethylation at approximately one third of the methylated CpG dyads. We hypothesize that the maintenance of DNA methylation may be less efficient at secondary differentially methylated sites than at primary imprinting control regions.

 

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This page is maintained by Tamara L. Davis/revised 7-3-2014.