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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
A comprehensive examination of topics in biochemistry, cell and molecular biology, and genetics. Lecture three hours, laboratory three hours a week.
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 101, 102 and Chemistry 103, 104.
Biology
372 - Molecular Biology (not offered 2008-2009; please see Biology 375/376)
This course will introduce students to molecular biology as a method for scientific inquiry. In addition to learning basic techniques for manipulation and analysis of nucleic acids, students will read and critically evaluate primary literature. Students will demonstrate knowledge of the material through written and laboratory work, class discussion and oral presentations. Lecture three hours, laboratory three hours a week. Prerequisites: Biology 201, 340 or 341; or permission of instructor.
Biology 375 - Integrated Biochemistry and Molecular Biology I
This course is the first semester in a two-semester course that focuses on the structure and function of proteins, carbohydrates, lipids and nucleic acids, enzyme kinetics, metabolic pathways, gene regulation and recombinant DNA techniques. Students will explore these topics via lecture, critical reading and discussion of primary literature and laboratory experimentation. Three hours of lecture, three hours of laboratory per week. Prerequisites: Two semesters of Introductory Biology and two semesters of Organic Chemistry.
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 375 - Integrated Biochemistry and Molecular Biology I, or permission of instructor.
Biology 393 - Senior Seminar in Molecular Genetics (not offered 2007-2008)
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 or permission of instructor.
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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.
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 have regions of differential methylation - for example, the silent paternal allele is methylated while the expressed maternal allele is unmethylated.
For proper imprinted expression to occur, the imprinting mark that differentiates the maternal and paternal alleles of a gene must be inherited at the time of fertilization. Therefore, the paternal and maternal patterns of methylation must be established during the development of the gametes (sperm and oocytes). It is important to understand that establishing the proper methylation pattern requires resetting one of the two alleles in every generation. This is because each individual must pass an appropriately marked allele on to his or her offspring. If a female must pass an unmethylated allele to her offspring, the methylation found on the allele she inherited from her own father must be removed during the formation of her oocytes. Similarly, if a male passes on a methylated allele to his offspring, the unmethylated allele he received from his mother must become methylated during the development of his sperm.
My research is focused on understanding when methylation
changes occur during gametogenesis. To do this, my lab analyzes
methylation patterns at imprinted genes during various stages of gamete
development in the mouse. Currently, we know the most about the
imprinted gene H19. Although the function of the H19
gene is unclear, it is one of the best-characterized imprinted genes. H19
is expressed from the unmethylated maternal allele, while the
methylated paternal allele remains silent. The region of
paternal-specific methylation is quite extensive, and it has been shown
that a 2000 base pair differentially methylated domain (DMD) is
required for proper imprinted expression. Our analysis of twelve
different stages during the development of the sperm led us to the
following conclusions:
My current research interests include analyzing the changes in methylation in the female germline, and analyzing other imprinted genes to determine if the methylation of all imprinted genes is coordinately regulated. To address these questions, we use molecular genetic techniques to isolate, amplify and analyze DNA.
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:
Christina Harview, class of 2009
Nelly Khaselev, class of 2011
Jane Morris, class of 2010
Mahvish Qureshi, class of 2010
Former research students
include:
Anna Arnaudo, class of 2002
Alison Best, class of 2003
Balpreet Bhogal, class of 2004
Meredith Calandra, class of 2004
Amber Carmo, class of 2001
Lauren Dockery, class of 2008
Alyson Dymkowski, class of 2004
Jennifer Gerfen, class of 2006
Lu Mei He, class of 2006
Rachel Horton, class of 2007
Sarah McCawley, class of 2002
Avery Miller, class of 2005
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
Charlotte Rahn-Lee, class of 2005
Lilah Rahn-Lee, class of 2005
Meghan Shayhorn, class of 2001
Geneva Stein, class of 2006
Ruthie Worrell, class of 2001
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.
The
following abstract will be presented as a poster at the 40th Annual Meeting of the Society for the Study of Reproduction, July 21-25, 2007, in Philadelphia, Pennsylvania.
Paternal allele-specific methylation at the imprinted mouse gene Rasgrf1 is present in both monoalleleic and biallelic tissues
Lauren Dockery* ('08), Rachel Horton* ('07), Jennifer Gerfen* ('06), Charlotte Rahn-Lee* ('05) and Tamara L. Davis
Department of Biology, Bryn Mawr College, Bryn Mawr, PA 19010-2899 USA
Genomic imprinting is a mammalian-specific phenomenon whereby genes are regulated such that only one of the two parental alleles is expressed. This monoallelic expression is frequently associated with parent of origin-specific epigenetic modifications, such as DNA methylation, histone methylation and histone acetylation. In mouse, the imprinted gene Rasgrf1 is expressed solely from the paternal allele in a some tissues, while in other tissues it is expressed from both parental alleles. Paternal allele-specific DNA methylation of the Ras-DMR, located approximately 30 kb 5’ relative to the Rasgrf1 transcriptional start site, is inherited from sperm. We have investigated the relationship between DNA methylation patterns and expression patterns at Rasgrf1 during embryonic development and in neonatal tissues. Our results demonstrate that paternal allele-specific methylation is retained in the blastocyst, indicating that differential methylation of the Ras-DMR can serve as the primary imprinting mark for Rasgrf1. In addition, we observed paternal allele-specific methylation in the placenta and head of an 8.5 days post coitum embryo, illustrating that both embryonic and extraembryonic tissues maintain the imprinting mark. Furthermore, we found paternal allele-specific methylation in all neonatal tissues examined, including tissues that have been reported to have monoallelic, biallelic and no expression of Rasgrf1. We conclude that while DNA methylation may play a role in marking the transcriptionally active paternal Rasgrf1 allele, it is not sufficient to induce monoallelic expression since tissues with biallelic expression also display paternal allele-specific methylation of the Ras-DMR. We are currently investigating the role histone modifications play in differentiating between the maternal and paternal Rasgrf1 alleles.
The following is the abstract from
a paper which was published in December 2004: Genomics 84(6): 961-970.
Methylation at mouse Cdkn1c is acquired during post-implantation
development and functions to maintain imprinted expression.
Balpreet Bhogal* ('04), Anna Arnaudo* ('02), Alyson Dymkowski* ('04),
Alison Best* ('03) and Tamara L. Davis
Monoallelic expression of imprinted genes is generally associated with
differential methylation. Methylation may be inherited as the gametic
imprinting mark or may be acquired post-fertilization. Here, we
characterize a differentially methylated region associated with the
mouse Cdkn1c gene and find that it is confined to a CpG island that
begins 600 bp 5' to the promoter and extends into the transcription
unit. Our analysis indicates that methylation of this region is not
inherited from sperm, is acquired specifically on the paternal allele
following implantation, and is dependent on KvDMR1. We further
demonstrate that although methylation is required for maintaining
silencing of the paternal Cdkn1c allele, it is not a pre-requisite for
the establishment of monoallelic expression at this locus. Prior to the
onset of differential methylation, additional epigenetic modifications
must play a role in distinguishing the parental alleles of Cdkn1c and
influencing their expression.
*denotes undergraduate student co-authors