PHS 398 (Rev. 9/04), Biographical Sketch Format Page s17

BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME POSITION TITLE Ravi Allada Professor eRA COMMONS USER NAME RAVIALLADA EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE INSTITUTION AND LOCATION (if YEAR(s) FIELD OF STUDY applicable) University of Michigan, Ann Arbor, MI B.S. 1985-1989 Biomedical Science 1989-1990, University of Michigan, Ann Arbor, MI M.D. Medicine 1992-1994 HHMI-NIH Research Scholar, National Institute Molecular Biology 1990-1992 of Mental Health, Bethesda, MD Mentor: Dr. Howard Nash

HHMI-NIH Continued Support Fellow Biochemistry 1994 National Cancer Institute, Bethesda, MD Mentor: Dr. Carl Wu 1994-5, Pathology Brigham and Women’s Hospital, Boston, MA A.B.P. 1999-2000 Mentor: Dr. Ramzi Cotran Genetics Howard Hughes Medical Institute/ Brandeis Post- 1995-2000 Mentor: Dr. Michael University, Waltham, MA Doc Rosbash

A. Personal Statement The goal of the proposed research is to examine the molecular mediators of neural activity rhythms in circadian pacemaker neurons using the fruit fly Drosophila and the mouse as model systems. To address this question, we will focus on a range of approaches from genetics to electrophysiology and behavior. My training and established track record of accomplishments in the areas of circadian clocks make me well qualified to conduct and supervise work in this proposal. My postdoctoral research training was in the area of Drosophila genetics of circadian rhythms in the laboratory of Dr. Michael Rosbash, where I cloned the Drosophila Clock gene. As an independent investigator at Northwestern University, my laboratory has identified and characterized novel components of the core circadian clock (CK2, clockwork orange) as well as those that are important for conveying temporal information to regulate behavior, including the PDF receptor and NA, the subject of this proposal. In addition, we have also been the only lab examining NA function in the circadian system. In addition to my background in the molecular and cellular bases of circadian behavior, my laboratory (in collaboration with Indira Raman) has pioneered the use of whole cell patch clamp physiology to analyze the function of adult Drosophila circadian pacemaker neurons, a technique showcased in this proposal. Our work has been recognized by a Burroughs Wellcome Career Award, a NARSAD Young Investigator Award, and as a Semifinalist in the HHMI Investigator Competition, and has also been published in highly cited journals such as Nature, Cell, Neuron, PLoS Biology, Current Biology and the Journal of Neuroscience. Having made substantial contributions to our understanding of how NA functions in the circadian network, we are exceptionally well positioned to further study this conserved ion channel as well as other channels critical to the function of circadian pacemaker neurons.

B. Positions and Honors Positions and Employment: 2000-2006 Assistant Professor, Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 2006-2010 Associate Professor, Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 2010-present Professor, Department of Neurobiology, and Pathology, Northwestern University, Evanston, IL 2012-present Chair, Department of Neurobiology, Northwestern University, Evanston, IL Honors and Awards: 1990 Howard Hughes Medical Institute Research Scholar 1992 Howard Hughes Medical Institute Fellowship for Continued Support 1993 Alpha Omega Alpha Honor Medical Society 1994 Hewlett-Packard Award 1995 National Research Service Award 1996 Chief Resident, Clinical Pathology, Brigham and Women's Hospital 1996 Howard Hughes Medical Institute Postdoctoral Research Fellowship for Physicians 1998 Paul E. Strandjord Young Investigator Award, Academy of Clinical Laboratory Physicians and Scientists 1999 Burroughs Wellcome Career Award in the Biomedical Sciences 2000 American Board of Pathology certification in Clinical Pathology 2003 Burroughs Wellcome Career Award, Outstanding Progress Report 2003 NARSAD Young Investigator Award 2007 Plenary Speaker, Drosophila Research Conference, Philadelphia, PA 2008 Howard Hughes Medical Institute Investigator Competition Semifinalist

Advisory Panels and Other Professional Activities: 2001 Panel member, NIH National Center on Sleep Disorder Research Workshop on “Neurobiology of Sleep and Waking: Implications for Insomnia” 2002-present Associate Director, Center for Sleep and Circadian Biology 2005, 2006 Ad hoc member, Neurogenesis and Cell Fate Study Section, special emphasis panel 2005-2009 Member, Biological Rhythms and Sleep (BRS) Study Section 2005-2010 Consultant and Chief Scientific Officer for NuNetix 2006, 2007 Ad hoc member, Neuroendocrinology, Neuroimmunology, and Behavior (NNB) Study Section 2010-present Member, College of CSR Reviewers

C. Selected peer-reviewed publications (15 out of 28 papers/20 reviews or chapters) Allada R, White NE, So WV, Hall JC, Rosbash M. (1998). A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless. Cell 93, 791-805. Commentary on this paper: Schibler U. (1998) Circadian rhythms: New cogwheels in the clockworks. Nature 393, 620-621. Lin J-M, Kilman VL, Keegan K, Paddock B, Emery-Le M, Rosbash M, and Allada R. (2002) A role for casein kinase 2a in the Drosophila circadian clock. Nature 420, 816-820. Commentary on this paper: Blau J. (2003) A new role for an old kinase: CK2 and the circadian clock. Nature Neurosci 6, 208-210. Zhao J, Kilman VL, Keegan KP, Ping Y, Emery P, Rosbash M, and Allada R (2003). Drosophila Clock can generate ectopic circadian clocks. Cell 113, 755-766. Commentary on this paper: Hastings MH. (2003) Circadian clocks: self-assembling oscillators? Current Biology 13, R681-R682. Campbell N. (2003) Clockwork conductor. Nature Reviews Genetics 4, 578. Pilcher HN. (2003) Flies get rhythm. Nature 423, 935. Lear BC, Merrill CE, Lin J-M, Schroeder A, Zhang L, and Allada R. (2005) A novel G-protein coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior. Neuron 48, 221-227 (featured on the cover) Commentary on this paper: Helfrich-Forster C. (2005) PDF has found its receptor. Neuron 48, 161-169. Holmes TC, Sheeba V. (2005) Circadian pathway: the other shoe drops. Curr Biol. 15:R987-989. Lear BC, Lin J-M, Keath JR, McGill JM, Raman IM, and Allada R. (2005) The ion channel narrow abdomen is critical to the neural output of the Drosophila circadian pacemaker. Neuron 48, 965-976. Pitman JL, McGill JJ, Keegan KP, and Allada R. (2006) A dynamic role for the mushroom bodies in promoting sleep in Drosophila. Nature 441, 753-756. Lim C, Chung BY, Pitman JL, McGill JJ, Pradhan S, Lee J, Keegan KP, Choe J, and Allada R. (2007) clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila. Current Biology 17,1082-1089. NIHSMID: NIHMS25930 Keegan K, Pradhan S, Wang JP, and Allada R. (2007) Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes. PLoS Computational Biology 3, e208. PMCID: PMC2098839 Commentary on this paper: Dolgin E. (2008) Unlocking the clock. The Scientist 22, 27. Chung BY, Kilman VL, Keath JR, Pitman JL, and Allada R (2009). The GABA(A) Receptor RDL Acts in Peptidergic PDF Neurons to Promote Sleep in Drosophila. Current Biology. 19(5):386-90. NIHSMID: NIHMS98054 Lear BC, Zhang L, Allada R (2009). The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior. PLoS Biol. 7(7):e1000154. PMID: 19621061. Zhang L, Lear BC, Seluzicki A, Allada R. (2009) The CRYPTOCHROME Photoreceptor Gates PDF Neuropeptide Signaling to Set Circadian Network Hierarchy in Drosophila. Current Biology, 19(23): 2050-5. NIHSMID: NIHMS157634 Allada R and Chung BY. (2010) Circadian organization of behavior and physiology in Drosophila. Annu Rev Physiol. 72: 605-624. PMCID: PMC2887282 Zhang L, Chung BY, Lear BC, Kilman VL, Liu Y, Mahesh G, Meissner RA, Hardin PE, Allada R. (2010) DN1(p) Circadian Neurons Coordinate Acute Light and PDF Inputs to Produce Robust Daily Behavior in Drosophila. Current Biology. 20(7) 591-9. PMCID: PMC2864127 Commentary on this paper: Choi C, Nitabach MN. Circadian biology: environmental regulation of a multi-oscillator network. Current Biology. 20(7): R322-324. Lim C, Lee J, Choi C, Kilman VL, Kim J, Park SM, Jang SK, Allada R* and Choe J* (*co-corresponding authors; 2011). The novel gene twenty-four defines a critical translational step in the Drosophila clock. Nature. 470(7334):399-403. PMCID: PMC3073513 Pfeiffenberger C and Allada R. (2012) Cul3 and the BTB Adaptor Insomniac Are Key Regulators of Sleep Homeostasis and a Dopamine Arousal Pathway in Drosophila. PLoS Genet 8(10): e1003003. doi:10.1371/journal.pgen.1003003. PMCID: PMC3464197

D. Research Support Active: D12AP00023 (PI: Allada, co-PI White, K.) 1/1/2012-2/28/2014 DARPA Using Temporal Phase Signatures to Predict and Control Biological Timing The goal of these studies is to elucidate the interactions between metabolic, circadian and aging timers using transcriptomics, translatomics, luminescence screening, and metabolite analysis under different environmental conditions.

R56NS052903 (P.I. Allada) in No Cost Extension 9/30/2011-8/31/2013 NINDS The Function of a Novel Conserved Ion Channel in Daily Behavior The goal of this bridge award is to examine the role of a novel ion channel in circadian rhythms and membrane excitability.

R01MH092273-01A (P.I. Allada; Co-PI Waddell) 6/1/2011-05/31/2016 NIMH Sleep Homeostasis, Plasticity and Memory The goal is to assess the effects of sleep deprivation on Mushroom Body (MB)-dependent learning and memory and MB synapses and to examine the link between learning and memory genes and sleep homeostasis, including a focus on their role in mediating the effects of sleep loss on learning and memory.

R01NS059042 (PI: Allada) 7/1/2008-6/30/2013 NIH Intercellular Signaling in the Circadian Clock The goal of these studies is to define the role of a neuropeptide receptor in circadian behavior and neural networks using tissue-specific rescue and knockdown, expression, signal transduction and genetic studies.

Completed (past three years): SG 2011-01 5/1/2011-4/30/2012 Brain Research Foundation Circadian Clocks and Neurodegeneration

R01NS052903-01, (PI: Allada) 9/1/2005-8/31/2009 NIH Function of the Novel Ion Channel na in Daily Rhythms