Current Appointment

Postdoctoral Associate

Advisor: Dr Stuart Schreiber
Chemical Biology Program
Broad Institute of MIT and Harvard
Cambridge, MA
Email: gill@broadinstitute.org

Research Interests

I am a postdoctoral researcher in the Center for the Science of Therapeutics at the Broad Institute and am interested in combining computational and chemical biological approaches to understand mechanisms of disease.

As a Ph.D. student in the joint UCSD/Salk Institute graduate program, I was interested in 24h rhythms in physiology (i.e., circadian rhythms), how they interact with the daily cycle of feeding/fasting, and how they are influenced by the external solar light/dark cycle. Using a paradigm called time-restricted feeding where the availability of food is confined to a few hours of the organism's wakeful hours, we demonstrated the explicit effect of the timing of caloric intake on metabolism, thereby tying disruption of diurnal rhythms, such as that seen in modern humans staying awake late into the night, to disease.

During grad school, I also worked on the developmental biology of the eye, in collaboration with GNF (Novartis) San Diego.

Education & Training

Research Associate (Postdoctoral)

2013-2014
The Salk Institute for Biological Studies
La Jolla, California, USA
Advisor: Dr Satchin Panda

 

Ph. D. in Biology

2006-2012
Division of Biological Sciences
University of California San Diego
La Jolla, California, USA
Advisor: Dr Satchin Panda

 

Visiting Scientist

2007-2010
[for a collaboration, while in the Salk/UCSD Ph.D. program]
Genomics Institute of the Novartis Research Foundation, San Diego

 

B. Tech. with Honors

2002-2006
Biotechnology and Biochemical Engineering
Indian Institute of Technology Kharagpur
West Bengal, India

Honors

1. Invited speaker, "From Cells to Clinic" Symposium, February 2014

2. Instructor, International Chronobiology Summer School, Vanderbilt University, Nashville, TN, July 2013

3. Postdoctoral Fellowship, Helmsley Center for Genomic Medicine, 2013

4. Best speaker award, CCB Fall Workshop on Biological Timing, November 2012

5. Bert and Ethel Aginsky Research Scholars Award, 2012

6. Chapman Scholar, H.A. and Mary K. Chapman Trust, 2011

Publications

(Listed in reverse chronological order. Click here to view these on PubMed.)

1. Gill S, Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits.
Cell Metabolism. November 2015 Download this paper

Abstract: A diurnal rhythm of eating-fasting promotes health, but the eating pattern of humans is rarely assessed. Using a mobile app, we monitored ingestion events in healthy adults with no shift-work for several days. Most subjects ate frequently and erratically throughout wakeful hours, and overnight fasting duration paralleled time in bed. There was a bias toward eating late, with an estimated <25% of calories being consumed before noon and >35% after 6 p.m. "Metabolic jetlag" resulting from weekday/weekend variation in eating pattern akin to travel across time zones was prevalent. The daily intake duration (95% interval) exceeded 14.75 hr for half of the cohort. When overweight individuals with >14 hr eating duration ate for only 10-11 hr daily for 16 weeks assisted by a data visualization (raster plot of dietary intake pattern, "feedogram") that we developed, they reduced body weight, reported being energetic, and improved sleep. Benefits persisted for a year.

 

2. Gill S, Le HD, Melkani GC, Panda S. Time-restricted feeding attenuates age-related cardiac decline in Drosophila.
Science. March 2015 Download this paper

Abstract: Circadian clocks orchestrate periods of rest or activity and feeding or fasting over the course of a 24-hour day and maintain homeostasis. To assess whether a consolidated 24-hour cycle of feeding and fasting can sustain health, we explored the effect of time-restricted feeding (TRF; food access limited to daytime 12 hours every day) on neural, peripheral, and cardiovascular physiology in Drosophila melanogaster. We detected improved sleep, prevention of body weight gain, and deceleration of cardiac aging under TRF, even when caloric intake and activity were unchanged. We used temporal gene expression profiling and validation through classical genetics to identify the TCP-1 ring complex (TRiC) chaperonin, the mitochondrial electron transport chain complexes, and the circadian clock as pathways mediating the benefits of TRF.

 

3. Hatori M#, Gill S#, Mure LS, Goulding M, O'Leary DDM, Panda S. Lhx1 maintains synchrony among circadian oscillator neurons of the SCN.
eLife. July 2014 Download this paper, Web server
#=equal contribution

Abstract: The robustness and limited plasticity of the master circadian clock in the suprachiasmatic nucleus (SCN) is attributed to strong intercellular communication among its constituent neurons. However, factors that specify this characteristic feature of the SCN are unknown. Here, we identified Lhx1 as a regulator of SCN coupling. A phase-shifting light pulse causes acute reduction in Lhx1 expression and of its target genes that participate in SCN coupling. Mice lacking Lhx1 in the SCN have intact circadian oscillators, but reduced levels of coupling factors. Consequently, the mice rapidly phase shift under a jet lag paradigm and their behavior rhythms gradually deteriorate under constant condition. Ex vivo recordings of the SCN from these mice showed rapid desynchronization of unit oscillators. Therefore, by regulating expression of genes mediating intercellular communication, Lhx1 imparts synchrony among SCN neurons and ensures consolidated rhythms of activity and rest that is resistant to photic noise.

 

4. Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA, Ellisman MH, Panda S. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet.
Cell Metabolism. June 2012 Download this paper, Web server

Abstract: While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

 

5. Gill S, Panda S. Feeding mistiming decreases reproductive fitness in flies.
Cell Metab. June 2011 Download this paper

Abstract: The diurnally active fruit flies prefer a major meal in the morning. Feeding the flies in the evening uncouples their metabolic cycle from circadian activity rhythms. A paper by Xu et al. in this issue of Cell Metabolism found that such uncoupled rhythms reduce egg laying.

 

6. Vollmers C, Gill S, DiTacchio L, Pulivarthy SR, Le HD, Panda S. Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
PNAS. Dec 2009 Download this paper, Web server

Abstract: In mammals, the circadian oscillator generates approximately 24-h rhythms in feeding behavior, even under constant environmental conditions. Livers of mice held under constant darkness exhibit circadian rhythm in abundance in up to 15% of expressed transcripts. Therefore, oscillations in hepatic transcripts could be driven by rhythmic food intake or sustained by the hepatic circadian oscillator, or a combination of both. To address this question, we used distinct feeding and fasting paradigms on wild-type (WT) and circadian clock-deficient mice. We monitored temporal patterns of feeding and hepatic transcription. Both food availability and the temporal pattern of feeding determined the repertoire, phase, and amplitude of the circadian transcriptome in WT liver. In the absence of feeding, only a small subset of transcripts continued to express circadian patterns. Conversely, temporally restricted feeding restored rhythmic transcription of hundreds of genes in oscillator-deficient mouse liver. Our findings show that both temporal pattern of food intake and the circadian clock drive rhythmic transcription, thereby highlighting temporal regulation of hepatic transcription as an emergent property of the circadian system.