Award details retrieved from the Center for Teaching & Faculty Excellence website.

What are the rules that govern connectivity, activity and robustness of neuronal networks that underlie fundamental behaviors?

Locomotion is a fundamental behavior shared by all animals and understanding its neuronal basis has been a major goal in neuroscience for many years. The nematode Caenorhabditis elegans is a particularly attractive model to study locomotion. It is the first multi-cellular organism to have its genome sequenced and the only animal that has a complete map of its cell lineage and nervous system. Recent technological breakthroughs, mainly in the fields of opto-genetics and opto-physiology respectively allow non-intrusively stimulating and recording from single cells as well as networks in vivo. I use these technologies to investigate the activity of all the elements of C. elegans locomotion network, composed of 75 neurons and 75 muscle cells, during locomotion.

Carl Woese Trumps Carl Linnaeus
Peter Mitchell Trumps Almost Everyone

Phylogeny and Bioenergetics have undergone “revolutionary” change in the past fifty years driven in large part by the work of two individuals who fought to change the paradigm and won, more or less.  These are examples from biology of Thomas Kuhn’s Scientific Revolutions, which Kuhn largely developed from physics.  This talk discusses the work of these two revolutionaries viewed from the perspective of interactions with the individuals concerned.

The computations performed by neural circuits are defined by the physiological properties of individual neurons and the synaptic connectivity amongst them. While ever more sophisticated methods to record and manipulate the physiology of neurons have appeared over the last few decades, methods for the anatomical reconstruction of synaptic connectivity have lagged behind. This is in large part due to the disparate length scales involved; the processes (including dendrites and axons) of neurons can be as thin as 50 nm and yet extend over many millimeters. The challenge of collecting enough data at synaptic resolution to encompass complete neuronal circuits can be overcome by automating both image acquisition and sectioning using serial block-face scanning electron microscopy (SBEM). I will briefly discuss the technical aspects of SBEM in relation to other current volume electron microscopy techniques and present some of the first neurobiological results using this technique. In particular, I will stress the power of combining functional recordings of neurons, such as two-photon excited fluorescence calcium imaging, with subsequent anatomical reconstruction of neuronal circuits in the mouse retina. I will also briefly discuss the next major challenge of how to efficiently analyze large (terabyte-sized) SBEM datasets.

A central problem in biology is to interpret the cellular responses to their complex and dynamic microenvironments and appropriately link them with their molecular profiles. Traditional biochemical approaches provide stochastic measurements as ensemble average of cell communities reflecting the biological mechanisms operating within the dominant subpopulation. However, at high enough resolution, multiscale heterogeneity is typically observed among individual cells. Microfluidics technology offers an ideal approach to offset current limitations and study such complex systems with the ability to manipulate cells on the individual basis. Interfacing the advanced microfluidic tools and assays with biology, we are investigating the heterogeneous aspect of human mammary epithelial cells (HMECs) in terms of proliferation, migration and signaling.

Despite the high degree of regulatory mechanisms involved in cell replication, abnormal cell cycles become fundamentally responsible for diseases such as cancer, alzheimer’s, aging etc. In both in vivo and in vitro models of the cell cycle analysis, the presence of multiple biochemical factors as well as physical cell-cell interactions not only obscures the origins of heterogeneity but also the functional relationships between cell cycle variations and their physiological/pathophysiological responses. We have utilized the micropatterning strategy to spatially and physiologically control cellular interactions with each other as well as with their microenvironment in desirable formats. A simplified array of cells patterned on a standard polystyrene plate with defined cell morphology, adhesion area and cell-to-cell spacing was developed to individually trigger the multitude of factors and correlate them with respective cellular responses. Through live cell imaging of the cell cycle and division (utilizing S/G2/M phase FUCCI fluorescent reporter), we have identified temporal differences in the cell cycle progression rates of HMECs acquired as a result of 1) Attachment area of cells with the tissue culture substrate and 2) Loss of contact inhibition due to intracellular interactions. Clonal population of cells originated from a single parent cell and synchronized to trigger the onset of their cell cycle acquired marked differences in their cycles when in contact with neighboring cells. By knocking out the transmembrane adhesion protein ‘E-cadherin’ on the cell surface, we anticipate to further narrow down the factors contributing to the loss of proliferation due to contact inhibition. These findings can be directly applied as a fundamental basis to study cancer cell dormancy and the interaction dynamics of metastatic circulating tumor cells and also provide a novel perspective for understanding cancer phenotypes undergoing uncontrolled cell growth.

Scientists and artists have always harnessed extraordinary gifts of curiosity and innovation as a guiding force for discovery.  Before the advent of the camera, scientists, like artists, utilized drawing and painting as a means of capturing and disseminating observations. This lecture will explore the concept of scientist as artist and the artist as scientist in a relationship to the development of my work, and will explore how the fields of art and science continue to inform and inspire each other.