Faculty & Research
 |
Johannes H. Bauer, Ph.D.Assistant ProfessorPh.D.: Free University of Berlin Postdoctoral training: |
Office: 238-DLS
Lab: 217-DLS Fly Lab:
319-DLS |
Research Interests
Molecular Mechanisms of Lifespan Regulation
A major research focus of the lab is the molecular dissection of signaling pathways that regulate longevity. We have recently shown that downregulation of the activity of the Drosophila melanogaster ortholog of the tumor suppressor p53, Dmp53, significantly extends fly longevity. Reduction of p53 activity was achieved by expressing dominant-negative (DN) versions of Dmp53 in the adult fly only. Expressing DN-Dmp53 in the adult nervous system, but not in other fly tissues, extended fly longevity by up to 26%. Furthermore, when DN-Dmp53 expression is restricted to a set of fourteen insulin-producing neurons (IPC), the same life span extension is observed.
Interestingly, DN-Dmp53 long-lived flies show a reduction in insulin/insulin-like signaling pathway (IIS) activity in their major metabolic organs, the fat body. Reduction of IIS activity has been shown to extend life span in nematodes, flies and mammals, even though the exact mechanisms remain unclear. However, when DN-Dmp53 is expressed in flies lacking dFoxo, a downstream mediator of IIS, lifespan is still extended. In contrast, the DN-Dmp53-dependent longevity increase is completely abolished in flies lacking 4E-BP, a downstream component of the TOR pathway. These data suggest that DN-Dmp53 utilizes TOR signaling to modulate longevity. We are currently investigating Dmp53 function inside the fourteen insulin-producing neurons and the events that lead to longevity extension.
In addition, in an attempt to dissect longevity signaling mechanisms
further downstream of IIS and TOR signaling, we have identified
takeout, a
Drosophila protein
involved in regulation of feeding behavior and sex determination.
Presently, we are characterizing the longevity phenotype and molecular
signaling mechanisms of takeout
expressing flies.
Development of Type 2 diabetes in Drosophila melanogaster
According to the CDC (National Diabetes Fact Sheet for 2007), approximately 7.8% of the U.S. population has diabetes, with a higher prevalence among minorities. In 2006, diabetes accounted for over 75,000 deaths, making it the 7th leading cause of death in the U.S. Complications associated with diabetes led to an additional ~230,000 deaths, mostly due to causing or aggravating other health conditions, such as heart disease, high blood pressure, stroke or neuropathies that can also lead to blindness. The treatment of diabetes and its symptoms has been estimated to cost $116 billion dollars in 2007 alone, with an additional $58 billion lost to disability, work loss or premature mortality (‘Economic costs of diabetes in the U.S. in 2007’, American Diabetes Association).
The realization that flies possess similar neuroendocrine cellular and molecular architecture as mammals has generated a lot of interest in utilizing flies as a cost-effective and rapid alternative to investigate molecular mechanisms of metabolic dysregulation. We are thus developing Drosophila as a cost-effective and rapid alternative model system for diabetes research. Drosophila has been spectacularly successful as a model system for a variety of human diseases, ranging from Alzheimer’s Disease to alcoholism. Advantages of the fly system are its rapid generation time and its low cost. However, the greatest strengths of the fly system are the powerful genetic tools that allow for rapid dissection of molecular disease mechanisms.
Work in our laboratory has demonstrated the development of diabetes-like
phenotypes in flies fed a western-style diet. Under these conditions
flies gain excessive weight, show metabolic abnormalities and develop
insulin-resistance in peripheral tissues. Similar phenotypes are
observed in aging flies. Importantly, anti-diabetic drugs reverse some
of these phenotypes.
With these benchmarks established, the Drosophila system can provide a
quick and inexpensive screening tool for pharmacologic and genetic
interventions that modify the diabetic phenotype.
Adult fat body cells stained with a marker for IIS activity. Strong plasma membrane staining indicates active IIS within these cells.
Undergraduate Research
BIOL 2101 - Introductory Research
This course takes place in a research laboratory. Students will be part of a team of scientists performing research into the molecular biology of the aging process. Successful completion of this course is a prerequisite for an independent undergraduate research project in the lab that may lead to admission to the Departmental Distinction Program.
Teaching
BIOL 5310 - Biological Chemistry
BIOL 5110 - Biological Chemistry Lab
Selected Publications
Antosh M, Whitaker R, Kroll A, Hosier S, Chang C,
Bauer J,
Cooper L, Neretti N, Helfand SL
(2011)
Comparative transcriptional pathway bioinformatic analysis of Dietary
Restriction, Sir2, p53 and resveratrol life span extension in
Drosophila.
Cell Cycle 10(6), in
press
Bauer J*,
Antosh M*, Chang C, Schorl C, Kolli S, Neretti N, Helfand SL
(2010)
Comparative transcriptional profiling identifies takeout as a gene that
regulates life span.
Aging
2(5): 298-310;
PMID: 20519778
Bauer JH,
Chang C, Bae G, Morris SN, Helfand SL
(2010) Dominant-negative Dmp53 extends life span
through the dTOR pathway in D. melanogaster.
Mech Ageing Dev 131(3):
193-201; NIHMS 20117129
Bauer JH,
Morris SN, Chang C, Flatt T, Wood JG, Helfand SL
(2009)
dSir2 and Dmp53 interact to mediate aspects of CR-dependent life span
extension in D. melanogaster.
Aging 1(1): 38-48; NIHMS 19851477
Bauer JH,
Chang C, Morris SN, Hozier S, Andersen S, Waitzman JS, Helfand SL
(2007)
Expression of dominant-negative Dmp53 in the adult fly brain inhibits
insulin signaling. Proc Natl
Acad Sci U S A 104(33): 13355-13360; NIHMS 17686972
Bauer JH, Poon PC, Glatt-Deeley H, Abrams JM, Helfand SL (2005) Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span. Curr Biol 15(22): 2063-2068; NIHMS 16303568
