The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

Our major research thrusts are to understand: 1) signals that engage the circadian clockwork in the brain, 2) sub-cellular micro-environments that shape neuronal dendrites in development and repair, and 3) emergent behaviors of integrated neuronal systems.

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 and alert? 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. This circadian clock, located in the suprachiasmatic nucleus (SCN) of the brain, whose cellular processes mark the passage of time in near 24-hr cycles, is a fundamental life component. Circadian clocks impose temporal order on cells, tissues and organs throughout the body, modulating 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 the role of the actin cytoskeleton in signaling and clock coupling 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.

Regarding neuroengineering development, we 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 types of functional cell clusters.

Representative Publications

Mitchell JW, Atkins N, Jr., Sweedler JV, Gillette MU. Direct cellular peptidomics of hypothalamic neurons. Front. Neuroendocrinology. vol. 32, #4, 377-386.

Wang Z, Millet LJ, Mir M, Ding, H. Unarunotai S, Rogers J, Gillette MU, Popescu G. Spatial light interference microscopy (SLIM). Optics Express. vol. 19, #2, pp 1016-1026.

Atkins N, Jr., Mitchell JW, Romanova EV, Morgan DJ, Cominski TP, Ecker JL, Pintar JE, Sweedler JV, Gillette MU. Circadian integration of glutamatergic signals by little SAAS in novel suprachiasmatic circuits. PLoS One. 2010 Sep 7; 5(9) e12612.

Ding H, Millet LJ, Gillette MU, Popescu G. Actin-driven cell dynamics probed by Fourier transform light scattering Biomedical Optics Express. Vol 1, Issue 1, pp 260-267 (2010).

Millet LJ, Stewart ME, Nuzzo RG, Gillette MU. Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices. Lab on a Chip. 10(12):1525-35. Epub 2010 Apr 13.

Ding H, Berl E, Wang Z, Millet LJ, Gillette MU, Liu J, Boppart M, Popescu G. Fourier transform light scattering of biological structures and dynamics. IEEE Journal of Selected Topics in Quantum Electronics 16 (4): 909-918.

Millet LJ, Bora A, Sweedler JV, Gillette MU. Direct cellular peptidomics of supraoptic magnocellular and hippocampal neurons in low-density co-cultures. ACS Chem Neuroscience. 1 (1): 36-48.

Gillette MU, Abbott SM. Biological Timekeeping. Sleep Med Clin. 4: 99-110.

Beaulé C, Mitchell JW, Lindberg PT, Damadzic R, Eiden LE, Gillette MU. Temporally restricted role of retinal PACAP: integration of the phase-advancing light signal to the SCN. J Biol Rhythms. 24(2):126-34.

Gillette MU, Tyan S-H. Circadian Gene Expression in the Suprachiasmatic Nucleus. Encyclopedia of Neuroscience 2:901-908.

Millet LJ, Stewart ME, Sweedler JV, Nuzzo RG, Gillette MU. Microfluidic devices for culturing primary mammalian neurons at low densities. Lab on a Chip. 7(8):987-94. Epub 2007 Jun 28.

Gillette MU, Sejnowski TJ. Biological clocks coordinately keep life on time. Science 309(5738):1196-8.

Tischkau SA, Mitchell JW, Pace LA, Barnes JW, Barnes JA, Gillette MU. Protein kinase G type II is required for night-to-day progression of the mammalian circadian clock. Neuron. 43(4):539-49.

Barnes JW, Tischkau SA, Barnes JA, Mitchell JW, Burgoon PW, Hickok JR, Gillette MU. Requirement of mammalian Timeless for circadian rhythmicity. Science 302(5644):439-42 -- Erratum in: Science. 2003 Nov 14;302(5648):1153

Tischkau SA, Mitchell JW, Tyan SH, Buchanan GF, Gillette MU. Ca2+/cAMP response element-binding protein (CREB)-dependent activation of Per1 is required for light-induced signaling in the suprachiasmatic nucleus circadian clock. J Biol Chem. 278(2):718-23. Epub 2002 Oct 29.

Gillette MU, Mitchell JW. Signaling in the suprachiasmatic nucleus: selectively responsive and integrative. Cell Tissue Res. 309(1):99-107. Epub 2002 Jun 6. Review.

Complete Publications List