Theodore Lindsay, PhD
thlindsay1 at gmail dot com
Machine Learning and Data Visualization
Excited by the opportunities and rapid pace of innovation in industry, I joined Insight Data Science as a fellow. Here I worked on a consulting project for Insight on a internal project where I developed a natural language search tool for their alumni slack network. This tool was built around a custom page-rank algorithm that I trained to identify question and answer sequences within the rather noisy conversations of the slack forums. You can read more about the approach I took here .
Along with my collaborators Floris Van Breugal and Peter Weir I worked on a project called figurefirst to enable agile construction of scientific figures. The main idea of figurefirst is to use the scalable vector graphics (SVG) language to specify a layout for a scientific figure. Figurefirst will parse this layout document and generate matplotlib plotting objects in python. This approach allows users to take advantage of SVG editors like inkscape to generate the layout and complex artwork, and then fuse these graphics with data-driven plotting code. Because the layout and plotting code can be developed independent of one another, it allows a much more iterative approach to figure creation where a scientist may start with a rough storyboard for a figure sequence using the layout, and then fill this out with data as analysis and experiments are completed.
I completed my postdoctoral training in the Dickinson Lab at the California Institute of Technology. Broadly my neuroscience intrests focused on how a nervous system endows an animal with agency in the world around it. To generate behavior, an animal's nervous system must respond to incoming sensory information and respond with the appropriate motor acts. This is a challenging problem since it requires neural networks that can decode a constant stream of information arriving from an array of diverse sensors; transform this information into motor commands that will produce a desired response; and do this within the constraints placed by the physics of the body. Moreover, this operation must be updated in real time, since the movement itself will change what the animal senses. Finally, the operation should account for the internal desires and intention of the animal: is it searching for food? courting a mate? defending a resource? recovering from illness of injury? I view behavior as the result of a continuous loop in which reaction is fused with intention, transformed into action that updates sensation.
I studied the neural elements of this loop at several levels, in several different model systems. Following my undergraduate degree, I investigated how sensory neurons of mice responded to the injury of bone and pancreatic cancer. For my doctoral work, I studied how the simple neural network of the nematode C. elegans might process noxious stimuli while the worm searches for food.
For my postdoc work, looked at a small set of motor neurons that the frutfly uses to steer in flight. To crack this problem I developed a technique that allows us to optically record the activity of this motor network in intact flies as they fly in a virtual reality flight simulator. This research identifed a simple combinatorial strategy that the fly uses to adjust wing motion, indicating that the biomechanical properties of the wing joint are setup to give the nervous system a robust mechanical system to control. This has broader implications in the neural control of motion, as it provides an example of how muscle physiology and biomechanics may be adapted not simply to optimize power or force, but also the neural control of these outputs.
Motor control of flight in flies
Biophysics of search and avoidance in nematodes
Ardiel E.L., Giles A.C., Alex J.Y., Lindsay T.H., Lockery S.R., Rankin C.H. Dopamine receptor DOP-4 modulates habituation to repetitive photoactivation of a C. elegans polymodal nociceptor. Learning & Memory. 2016 Oct 1;23(10):495-503.
Roberts, W.M., Augustine, S.B., Lawton, K.J., Lindsay, T.H., Thiele, T.R., Izquierdo, E.J., Faumont S., Lindsay, R.A., Britton, M.C., Pokala, N.,Bargmann, C.I., Lockery, S.R., A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans. eLife. 2016 Jan 29;5:e12572.
Lockery S.R., Hulme S.E., Roberts W.M., Robinson K.J., Laromaine A, Lindsay T.H., Whitesides G.M., Weeks J.C. A microfluidic device for whole-animal drug screening using electrophysiological measures in the nematode C. elegans. Lab Chip 12, 2211–2220 (2012).
Neurochemistry of cancer pain in mice
Sevcik M.A., Jonas B.M., Lindsay T.H.*, Halvorson K.G., Ghilardi J.R., Kuskowski M.A., Mukherjee P., Maggio J.E., Mantyh P.W. Endogenous opioids inhibit early-stage pancreatic pain in a mouse model of pancreatic cancer. Gastroenterology 131, 900–910 (2006).
Lindsay T.H., Jonas B.M., Sevcik M.A., Kubota K., Halvorson K.G., Ghilardi J.R., Kuskowski M.A., Stelow E.B., Mukherjee P., Gendler S., Wong GY., Mantyh P.W. A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas. Neuroscience 137, 1417–1426 (2006).
Lindsay T.H., Jonas B.M., Sevcik M.A., Kubota K., Halvorson K.G., Ghilardi J.R., Kuskowski M.A., Stelow E.B., Mukherjee P., Gendler S., Wong GY., Mantyh P.W. Pancreatic cancer pain and its correlation with changes in tumor vasculature, macrophage infiltration, neuronal innervation, body weight and disease progression. Pain 119, 233–246 (2005).
Sevcik M.A., Ghilardi J.R., Peters C.M., Lindsay T.H., Halvorson K.G., Jonas B.M., Kubota K., Kuskowski M.A., Boustany L., Shelton D.L., Mantyh P.W. Analgesic efficacy of bradykinin B1 antagonists in a murine bone cancer pain model. J Pain 6, 771–775 (2005).
Halvorson K.G., Kubota K., Sevcik M.A., Lindsay T.H., Sotillo J.E., Ghilardi J.R., Rosol T.J., Boustany L., Shelton D.L., Mantyh P.W. A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone. Cancer Res. 65, 9426–9435 (2005).
Sevcik M.A., Ghilardi J.R., Peters C.M., Lindsay T.H., Halvorson K.G., Jonas B.M., Kubota K., Kuskowski M.A., Boustany L., Shelton D.L., Mantyh P.W. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain 115, 128–141 (2005).
Ghilardi J.R., Rorhrich H., Lindsay T.H., Sevcik M.A., Schwei M.J., Kubota K., Halvorson K.G., Poblete J., Chaplan S.R., Dubin A.E., Carruthers N.I., Swanson D., Kuskowski M., Flores C.M., Julius D., Mantyh P,W. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J. Neurosci. 25, 3126–3131 (2005).
Peters, C.M., Ghilardi, J.R., Keyser, C.P., Kubota, K., Lindsay, T.H., Luger, N.M., Mach, D.B., Schwei, M.J., Sevcik, M.A., Mantyh, P.W. Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain. Exp. Neurol. 193, 85–100 (2005).
Peters, C.M., Lindsay, T.H., Pomonis, J.D., Luger, N.M., Ghilardi, J.R., Sevcik, M.A., Manyh, P.W. Endothelin and the tumorigenic component of bone cancer pain. Neuroscience 126, 1043–1052 (2004).