Portal to the Penn Neuroscience Community

Home

MINS Members

MINS News

Weekly Events

MINS Colloquium Schedule

History

Community Outreach Programs

Neuroscience Graduate Group
Other Educational Activities

Society for Neuroscience

Classified Ads

 MINS Members

Amita Sehgal, Ph.D.

Professor
Howard Hughes Medical Institute
Dept of Neuroscience
School of Medicine
233 Stemmler Hall/6074
(215) 573-2985, Lab: (215) 898-1177
FAX: (215) 573-2015
email:   amita@mail.med.upenn.edu

Click here for selected publications since Dr. Sehgal's arrival at Penn

RESEARCH INTERESTS

RESEARCH TECHNIQUES

RESEARCH SUMMARY

The overall goal of our research is to understand the molecular basis of behavior. The focus has been on cyclic behavior that occurs with a circadian (~24 hour) periodicity. Using the fruit fly Drosophila melanogaster, we and others have characterized a "molecular clock" that requires products of the period (per) and timeless (tim) genes. Levels of per and tim RNA and protein cycle with a circadian period and the two proteins feedback inhibit the synthesis of both mRNAs,thereby generating an autoregulatory loop. We have shown that cycling of the two proteins is critical for rhythmic rest:activity and can even by maintained in the absence of mRNA cycling, most likely through rhythmic activity of phosphatases. These timekeeping mechanisms, first identified in Drosophila , are found to be conserved in mammals. We have also uncovered mechanisms that synchronize the clock to light, starting with the demonstration that the tim protein (TIM) is degraded in response to light and including the most recent discovery of a protein, jet-lag, that targets TIM for degradation. We have also identified components of the pathway that transmit timekeeping signals from the clock and result in rhythmic rest:activity. The Drosophila homolog of the Neurofibromatosis 1 (NF1) gene is one such output gene. In addition, we have examined the effects of clocks in peripheral (non-brain) tissues on other aspects of physiology.

We also developed the fly as a model system for sleep. We showed that the rest phase in flies is a sleeplike state, and can be used to study not only circadian regulation, but also the homeostatic control of sleep, in other words the essential need for sleep. Using the fly model, we have identified molecular components as well as cellular loci that regulate sleep. An important sleep-regulating locus in the fly is the mushroom body, site of learning and memory in the fly. We have also identified effects of aging upon sleep and circadian rhythms.

KEY WORDS:

The Sehgal Lab