Thomas A. Jongens, Ph.D.
Associate Professor, Dept of Genetics

Genetics and Gene Regulation Program

Address


538A Clinical Research Building
415 Curie Boulevard
Philadelphia PA 19104-6100

office - 215 573-9332
lab -215 573-9386
Fax: 215 573-9411
E-mail: jongens@mail.med.upenn.edu

Link(s)

Dr Jongens at the Dept of Genetics

Education

University of California, San Diego, B.A. (Biochemistry/Cell Biology),1983

University of California, Berkeley, Ph.D. (Molecular Biology), 1989

Research Interests

• Modeling Fragile X Mental Retardation in Drosophila; Germ Cell Specification

Key words Fragile X Syndrome, RNA binding proteins, localized translation, germ cells, transcriptional repression, chromatin reorganization, germline.

Search PubMed for articles

Description of Research

Fragile X Modelling:

Fragile X syndrome is the most commonly inherited form of mental retardation. It is due to the loss of FMR gene function. Initial characterization of the FMR protein has shown that it is an RNA binding protein, with specificity for a subpopulation of mRNAs within neurons. The Drosophila genome contains a single gene that is highly homologous to the FMR1 gene. It is called dfmr1. We have developed a Drosophila Model to Study Fragile X Syndrome, based on dfmr1 mutants. Interestingly, this model displays several behaviorial phenotypes that bear similarity to the symptoms of Fragile X patients. These include circadian defects, short term memory defects, attention deficit and period of hyperactivity. In addition, the fly model displays neuronal defects that are similar to neuronal defects found in the brains of Fragile X patients. We are using genetic, molecular and biochemical studies to identify the substrate mRNAs regulated by dFMR1 proteins that lead to the observed behavioral defects. Results in this model will provide insight into the cause of Fragile X syndrome in humans.

Germ Cell Specification:

The germ cell has the most developmental potential of any other cell type as it is the only one capable of giving rise to a complete organism. We are studying how germ cell precursors are specified during development to understand how they retain their developmental "totipotency". In Drosophila , like organisms ranging from worms to frogs, the germ cell precursors are specified by germ plasm, a specialized cytoplasm localized within the egg. Our goal is to identify the germ plasm components which specify germ cell fate and determine the molecular mechanism by which they do so. One gene that we are focusing on is germ cell-less which is required for and capable of initiating some of events of germ cell precursor formation. We have found that the germ cell-less gene acts to repress transcription in the germ cell precursors. This is a vital to their proper development. We are currently trying to determine how the Germ Cell-less protein acts to repress transcription. This is an interesting question because we know that the Germ Cell-less protein is localized to the nuclear envelope. Our current model is that Germ Cell-less protein binds to DNA proteins, localizing them and the DNA they bind to to the nuclear envelope, thus repressing transcription. This model is based on the finding that Germ Cell-less protein binds to DNA binding proteins and telomeric sequences are known to be transcriptionally repressed by their localization to the nuclear envelope.

Recent Publications

McBride SM, Choi CH, Wang Y, Liebelt D, Braunstein E, Ferreiro D, Sehgal A, Siwicki KK, Dockendorff TC, Nguyen HT, McDonald TV, Jongens TA. Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile x syndrome. Neuron. 45, 753-64 (2005).

Costa A, Wang Y, Dockendorff TC, Erdjument-Bromage H, Tempst P, Schedl P, Jongens TA. The Drosophila Fragile X Protein Functions as a Negative Regulator in the orb Autoregulatory Pathway. Dev Cell. 8, 331 42 (2005).

Jin P, Zarnescu D.C, Ceman S., Nakamoto M., MowreyJ., Jongens T.A., Nelson D.L, Moses K., Warren S.T. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci. 7, 113-7 (2004).

Leatherman, J.L., Levin, L., Boero, J., Jongens, T.A.: Germ cell-less acts to repress transcription during the establishment of the Drosophila germ cell lineage. Curr. Biol. 12, 1681-1685, 2002.

Dockendorff, T.C., Su, H.S., McBride, S.M.J., Yang, Z., Choi, C.H., Siwicki, K.K., Sehgal, A. and Jongens, T. A. :Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron 34, 973-984, 2002.

Lab

Rotation Projects

The following is a list of some of the available rotation projects:

Fragile X Modelling:
Microarray studies of RNA copurifying with the dFMR1 protein; genetic interaction studies with putative targets of dfmr1 activity;further characterization of behavioral and neuronal phenotypes, characterization of proteins that interact with the dFMR1 protein.

Germ Cell project:
DNA in situ analysis to determine if regions of DNA are localized to the nuclear envelope by the Germ Cell-less protein; Characterization of a novel DNA binding protein that binds to Germ Cell-less protein. Immuno-colocalization studies to demonstrate that Germ Cell-less protein interacts transcription factors in vivo.

Lab personnel:

Pepper, Anita - Postdoc
aspepper@mail.med.upenn.edu

Wang, Yan - Postdoc
yanw@mail.med.upenn.edu

Bhogal, Balpreet - Graduate Student
bbhogal@mail.med.upenn.edu

Beerman, Rebecca - Graduate Student
rbeerman@mail.med.upenn.edu

Chiorean, Stephanie -Tech
seadrian@mail.med.upenn.edu