618 Morrill Hall
Lab: 217-244-1842; 217-333-4561
Cell & Developmental Biology, MC123
601 South Goodwin Avenue
Urbana, IL 61801
• The neurobiology of time: circadian regulation of neuronal and glial plasticity in the hippocampal dentate gyrus and suprachiasmatic nucleus • Nanoscale processes of dendrogenesis, neural network formation/regeneration • Emergent behaviors of integrated cellular systems
Our major research thrusts are to understand: 1) signals that engage the circadian clockwork in neurons and glia of the hippocampus and suprachiasmatic nucleus, 2) sub-cellular micro-environments that shape neuronal dendrites in development/regeneration, and 3) emergent behaviors of integrated neuronal systems. We use approaches ranging from physiology and cell biology to neuroengineering.
Regarding the neurobiology of time, consider these observations. Why do birds sing in the morning, while frogs call at night? Why are heart attacks likely to strike before dawn, while asthmatic attacks generally occur after sunset? Why do we most often feel lethargic and depressed during the short, dark days of winter, while on long, sunny summer days, we feel energetic, alert, aware? The answer to each of these questions lies in understanding the central role of the brain's clock in organizing our body functions around the major variable in the external world, the daily cycle of darkness and light.
We study circadian clocks in both the HIPPOCAMPUS and suprachiasmatic nucleus (SCN). Cellular and local network processes mark the passage of time in near 24-hr cycles, a fundamental life component. Circadian clocks impose temporal order on cells, tissues and organs throughout the body, modulating brain and body processes over the day-night cycle. Our broad research objective is to understand how biological timing systems control integrative brain functions. Our focus is on astrocytes-neuron interactions in signaling and cell-cell interactions via peptides.
This major research thrust has important applications: Malfunctioning of the brain's circadian clock results in disorders in brain and organ function, which manifest themselves as clinical disorders of sleep, movement and neural degeneration, such as in Alzheimer's and Parkinson's diseases. The breadth of our systems-based analysis is generating insights into mechanisms that synchronize people to day and night, which is of proven importance to good health and disease-resistance. Outcomes will enhance understanding of substrates that generate long-term neural changes, with broad relevance for public health and disease prevention. They will enable strategies for ameliorating sleep, autonomic, degenerative, movement and cognitive disorders.
Studies of developing/regenerating dendrites are building upon campus excellence in molecular and cellular biology, nano-scale analytical chemistry, and bioengineering. We study signals that shape the outgrowth of neuronal protrusions that wire the nervous system. Our goal is to discover novel insights, solutions, and applications for neural repair and restoration of function through targeting critical molecules and processes that construct micro-networks during the normal wiring of the nervous system.
Regarding emergent behaviors of neuronal clusters, we are controlling microenvironments to understand and direct the sensing, integration and actuation properties of neurons and their interactions with other functional types of cellular clusters.
Jonathan Sweedler (Chemistry, Bioengineering) - Peptidomics and metabolomics of the dentate gyrus and suprachiasmatic nucleus; census of cellular heterogeneity of the dentate gyrus
Rohit Barghava (Bioengineering) - Census of cellular and tissue heteterogeneity in the dentate gyrus via Scattered Raman Spectroscopy
Hyunjoon Kong (Chemical & Biomolecular Engineering) - Engineering 3D microenvironments for neuronal network formation and regeneration
Gabriel Popescu (Electrical & Computer Engineering) - Dynamics and emergent properties of neuronal circuits in real time using innovative imaging
Xuling Li (Electrical & Computer Engineering) - Toward intelligent synthetic neural circuits: Directing and accelerating neuron cell growth by self-rolled-up silicon nitride microtube array
Taher Saif (Mechanical Engineering) - Engineering neuronal components for contractile biological machines
Parijat Sengupta (Bioengineering) - Optogenetic regulation of neurons & glia
Yanyan Wang (Pharmacology) - LTP in aged mice
Aging, Cell Signaling and Communication, Development, Learning, Memory, and Plasticity, Molecular Neuroscience, Neuroengineering, Neurological and Psychiatric Conditions, Nutritional Neuroscience, Sensory and Motor Systems
NIH 1U01MH109062 Sweedler (PI), Gillette, Bhargava 9/18/15 – 6/30/2018 BRAIN Innovation Grant: Integrated Multimodal Analysis of Cell and Circuit-Specific Processes in Hippocampal Function
NSF STC CBET 0939511 Kamm - BioE/MechE, MIT (PI) 9/15/10-9/14/2020 Science & Technology Center: Emergent Behaviors of Integrated Cellular Systems (EBICS), with MIT & Georgia Tech and UCMerced, Morehouse College, CCNY
ABBOTT CNLM 2015-06958 Gillette (PI), Sweedler 8/16/15-12/31/2016 Diet-Modified Neuron Physiology Assessments
NSF DBI 1450962 EAGER Gillette (PI), Popescu, Rogers, Sweedler 9/01/14 – 8/31/2016 BRAIN EAGER: Multiscale Dynamics and Emergent Properties of Suprachiasmatic Circuits in Real Time
ABBOTT CNLM 2014-07443 Sweedler (PI), Gillette, Rhodes 8/15/14-7l/15/2016 Diet-Modified Brain Chemistry and Plasticity: Nutrition as a Case Study
NSF IOS 1354913 Gillette (PI) 6/15/14 – 6/14/2018 Regulation of SCN Glial Plasticity
P30 DA018310 Sweedler (PI), Gillette (Center User) 6/2009- 6/2019 NIH (NIDA) Proteomics & Technology Center Initiative Neuroproteomics Center on Cell-Cell Signaling
NSF CBET 1403660 Boppart (PI), Gillette 4/01/14 – 3/31/2017 Enhanced Optogenetic Control of Neuronal Activity with Tailored Light Stimuli
NIH R21 MH101655 Gillette (PI) 7/01/13-6/30/16 High-Resolution Analysis of miR125b in Dendrites via Microfluidic Devices
Lee, M.K., M.H. Rich, A. Shkumatov, J.H. Jeong, M.D. Boppart, R. Bashir, M.U. Gillette, J. Lee, H. Kong. 2015. Glacier moraine formation-mimicking colloidal particle assembly in microchanneled, Bbioactive hydrogel for guided vascular network construction. Adv. Healthcare. Materials. 2015 Jan 4 (2):195-201. Epub 2014 Jun 4. doi: 10.1002/adhm.201400153. [Epub ahead of print] PMID: 24898521; PMCID: PMC Journal - In Process
Yang, N., S.J. Irving, E.V. Romanova, J.W. Mitchell, M.U. Gillette, J.V. Sweedler. 2015. Neuropeptidomics: the characterization of neuropeptides and hormones in the nervous and neuroendocrine systems. International Neuroendocrine Federation (INF) Masterclass Series: "Molecular Neuroendocrinology.” In press.
Jain, A. and M.U. Gillette. 2015. Development of microfluidic devices for the manipulation of neuronal synapses. In: Microfluidic and Compartmentalized Platforms for Neurobiological Research: Neuromethods 103, Emilia Biffi, Ed., Wolfgang Walz, Editor-in-Chief, v. 103 Springer Science+Business Media New York, pp. 127-137.
Froeter, P., Y. Huang Y, O.V. Cangellaris, W. Huang, E.W. Dent, M.U. Gillette, J.C. Williams, X. Li. 2014. Toward intelligent synthetic neural circuits: directing and accelerating neuron cell growth by self-rolled-up silicon nitride microtube array. ACS Nano. 2014 Nov 25; 8(11):11108-17. doi: 10.1021/nn504876y. Epub 2014 Nov 3. PMCID: PMC4246008
Iyer, R., T.A. Wang, M.U. Gillette. 2014. Circadian gating of neuronal functionality: a basis for iterative metaplasticity. In "Sleep and Circadian Rhythms in Plasticity and Memory,” J. Gerstner, H.C. Heller, S. Aton, Eds. Front. Systems Neurosci. 2014 September 19 8: 164, 14 pp; doi: 10.3389/fnsys.2014.00164. [Epub ahead of print]. PMCID: PMC4168688
Southey, B.R., J.E. Lee, L. Zamdborg, N. Atkins, Jr., J,W. Mitchell, M. Li, M.U. Gillette, N.L. Kelleher, J.V. Sweedler. 2014. Comparing label-free quantitative peptidomics approaches to characterize diurnal variation of peptides in the rat suprachiasmatic nucleus. Anal. Chem. 86(1): 443–452. PMCID: PMC3886391
Mir, M., T. Kim, A. Majumder, M. Xiang, R. Wang, S.C. Liu, M.U. Gillette, S. Stice, and G. Popescu. 2014. Label-free characterization of self-organizing human neuronal networks. Scientific Reports 4: 4434 (8 pg). PMCID: PMC3963031
Gillette, M.U. and T.A. Wang. 2014. Brain oscillators and redox regulation in mammals. In Forum Issue on “Circadian clocks and redox signaling,” A. Reddy, Ed. Antioxidants & Redox Signaling (ARS) 2014 Feb10; 20(17): 2955-2965. [Epub ahead of print]. PMCID: PMC4038987
Abbott, S.M., J.M. Arnold, Q. Chang, H. Miao, N. Ota, C. Cecala, P.E. Gold, J.V. Sweedler, M.U. Gillette. 2013. Signals from the brainstem arousal centers regulate behavioral timing via the circadian clock. PLoS One. Aug 12; 8(8): e70481. PMCID: PMC3741311
Lee J.E, L. Zamdborg, B. Southey, N. Atkins, Jr., J.W. Mitchell, M. Li, M.U. Gillette, N.L. Kelleher, J.V. Sweedler. 2013. Quantitative peptidomics for discovery of circadian-related peptides from the rat suprachiasmatic nucleus. J. Proteome Res. 2013 Feb 1; 12(2): 585-93. Epub 2013 Jan 11. PMCID #3562399
Gillette, M.U., Editor. 2013. Chronobiology: Biological Timing in Health and Disease, v. 119 Progress in Molecular Biology and Translational Science, Editor-in-Chief Michael Conn for Academic Press (an imprint of Elsevier).
Wang, T.A., Y.V. Yu, G. Govindaiah, X. Ye, L. Artinian, T.P. Coleman, J.V. Sweedler, C.L. Cox, M.U. Gillette. 2012. Circadian rhythm of redox state non-transcriptionally regulates excitability in suprachiasmatic nucleus neurons. Science. 2012 Aug 17; 337(6096): 839-42. Epub 2012 Aug 2. http://www.sciencemag.org/content/337/6096/839.full.pdf Perspective: Circadian Time Reduxed. http://www.sciencemag.org/content/337/6096/805.full.pdf. PMCID: PMC3490628
Yin P., A.M. Knolhoff, H.J. Rosenberg, L.J. Millet, M.U. Gillette, J.V. Sweedler. 2012. Peptidomics analysis of astrocyte secretion. J. Proteome Res. 2012 Aug 3; 11(8): 3965-73. Epub 2012 Jul 16. PMCID: PMC3434970
Govindaiah G, T.A. Wang, M.U. Gillette, C.L. Cox. 2012. Activity-dependent regulation of retinogeniculate signaling by metabotropic glutamate receptors. J. Neuroscience. 2012 Sep 12; 32(37): 12820-31. PMCID: PMC3462222
Millet, L.J. and M.U. Gillette. 2012. New perspectives on neuronal development using microfluidic environments. Trends in Neuroscience. 2012 Dec; 35(12): 752-61. Epub 2012 Sep 29. PMCID: PMC3508261
Millet, L.J., M.U. Gillette. 2012. Over a century of neuron culture: From the hanging drop to microfluidic devices. Yale J. Biol. Med. 2012 Dec; 85(4): 501-21. Epub 2012 Dec 13. PMCID: PMC3516892 Cecala, C., S.S. Rubakhin, J.W. Mitchell, M.U. Gillette, J.V. Sweedler. 2012. A hyphenated optical trap capillary electrophoresis laser induced native fluorescence system for single-cell chemical analysis. Analyst. 2012 Jul 7; 137(13): 2965-72. PMCID: PMC558031
Gillette, M.U., S.M. Abbott, and J. M. Arnold. 2012. Biological timekeeping. In: Sleep Medical Clinics, Biology of Sleep, Guest Edited by T. Lee-Chiong. (2012 September) 7(3), 427-442.
Murphy, David. A. Konopacka, C. Hindmarch, J.F.R. Paton, J.V. Sweedler, M.U. Gillette, Y. Ueta, V. Grinevich, M. Lozic, N. Japundzic-Zigon. 2012. The Hypothalamo-Neurohypophyseal System: from Genome to Physiology. J. Neuroendocrinol. 2012, April; 24 (4): 539-553. PMCID: PMC3315060
Mitchell, J.W., N. Atkins, Jr., J.V. Sweedler, M.U. Gillette. 2011. Direct cellular peptidomics of hypothalamic neurons. Front. Neuroendocrinol. Invited review. 32(4): 377-386. PMCID: PMC3165142
Wang, Z., D. L. Marks, P. S. Carney, L. J. Millet, M.U. Gillette, A. Mihi, P. V. Braun, Z. Shen, S. G. Prasanth, G. Popescu. 2011. Spatial light interference tomography (SLIT). Optics Express. 19 (21): 20571-20579. PMCID: PMC3495874
Wang, R., Z. Wang, L. Millet, M.U. Gillette, G. Popescu. 2011. Dispersion-relation phase spectroscopy of intracellular transport. Optics Express. 19 (21): 20571-20579. PMCID: PMC3495870
Wang, Z., L. Millet, H. Ding, M. Mir, S. Unarunotai, J. Rogers, M.U. Gillette, G. Popescu. 2011. Spatial light interference microscopy (SLIM). Optics Express. 19 (2): 1016-1026. PMCID: PMC3482902
Wang, R, Z. Wang, J. Leigh, N. Sobh, L. Millet, M.U. Gillette, A. Levine, G. Popescu. 2011. One-dimensional deterministic transport in neurons measured by dispersion-relation phase spectroscopy. J. Phys. Condens. Matter. 23 (2011): 374107 (Supp). PMCID: PMC3195397
Wang, Z., L.J. Millet, V. Chan, H. Ding, M.U. Gillette, R. Bashir, G. Popescu. 2011. Label-free intracellular transport measured by Spatial Light Interference Microscopy (SLIM). J. Biomed Opt. 16(2): 026019. PMCID: PMC3071305
Shepherd, J.N., S.T. Parker, R.F. Shepherd, M.U. Gillette, J.A. Lewis and R.G. Nuzzo. 2011. 3D microperiodic hydrogel scaffolds for robust neuronal cultures. Adv. Funct. Mater. 21(9): 47-54. DOI: 10.1002/adfm.2010.01746, PMCID: PMC3120232
Ding, H., L.J. Millet, R. Iyer, M.U. Gillette and G. Popescu 2010. Actin-driven cell membrane fluctuations probed by Fourier transform light scattering. Biomed. Opt. Express. 1(1): 260-267. PMCID: PMC3005177
Ding, H., E. Berl, Z. Wang, L.J. Millet, M.U. Gillette, J. Liu, M. Boppart and G. Popescu. 2010. Fourier transform light scattering of biological structures and dynamics. IEEE J. Sel. Top. Quantum Electron. 16(4): 909-918. doi: 10.1109/JSTQE.2009.2034752. No PMID
Govindaiah, G., T.A. Wang, M.U. Gillette, S.R. Crandall and C.L. Cox. 2010. Regulation of inhibitory synapses by presynaptic D4 dopamine receptors. J. Neurophysiol. 2010 Nov; 104(5): 2757-65. PMCID: PMC2997036
Ding, H, Z. Wang, F.T. Nguyen, S.A. Boppart, L.J. Millet, M.U. Gillette, J. Liu, M. Boppart, G. Popescu. 2010. Fourier transform light scattering (FTLS) of cells and tissues. J. Comput. Theor. Nanosci. 7(12): 2501-2511. doi: 10.1166/jctn.2010.1637. No PMID.
Atkins N., Jr., Mitchell J.W., Romanova E.V., Morgan D.J., Cominski T.P., Ecker J.L., Pintar J.E., Sweedler J.V., Gillette M.U. 2010. Circadian integration of glutamatergic signals by little SAAS in novel suprachiasmatic circuits. PLoS One 5(9): e12612.
Millet L.J., Stewart M.E., Nuzzo R.G., Gillette M.U. 2010. Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices. Lab on a Chip 10(12):1525-35.
Gillette, M.U., Tyan S-H. Circadian Gene Expression in the Suprachiasmatic Nucleus. 2009. Encyclopedia of Neuroscience 2:901-908.
Wang, Z., Millet, L. J., Gillette, M. U., Popescu, G. 2008. Jones phase microscopy of transparent and anisotropic samples. Optics Letters 33, 1270-2.
Gillette MU, and Sejnowski TJ 2005. Physiology. Biological clocks coordinately keep life on time. Science 309(5738):1196-8.
Buchanan GF, and Gillette MU. 2005. New light on an old paradox: site-dependent effects of carbachol on circadian rhythms. Exp Neurol. 193(2):489-96.
Tischkau SA, and Gillette MU. 2005. Oligodeoxynucleotide methods for analyzing the circadian clock in the suprachiasmatic nucleus. Methods Enzymol. 393:593-610.
Turek, F.W., Gillette, M.U. 2004. Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists. Sleep Med. 5(6):523-32
Gillette, M.U. 2004. Does the SCN regulate more than sleep timing? Sleep 27(7):1240-1.
Tischkau SA, Mitchell JW, Pace LA, Barnes JW, Barnes JA, and Gillette MU. 2004. Protein kinase G type II is required for night-to-day progression of the mammalian circadian clock. Neuron 43(4):539-49.