Elizabeth Heckscher | Committee on Genetics, Genomics and Systems Biology

Research Summary

My lab studies the assembly and function of sensorimotor circuits. Sensorimotor circuits, such as those found in the human spinal cord, are required for all behavior. These circuits perform functions unique from those of other brain regions. They process a variety of somatosensory stimuli such as heat, light-touch, pain, and self-movement. These circuits generate patterned muscle contractions that are specifically tuned to allow animals to move in a changing environment. Movement control- My lab is interested in understanding how neural circuits implement the motor programs that allow animals to move. Our goal is to understand the functional architecture of a sensorimotor system at the cellular level. Circuit assembly- We are also interested in understanding the developmental logic of that explains how sensorimotor circuits form. Our goal is to understand how developmental history impacts circuit assembly: what is the role in functional circuit development of lineage, neuronal birth timing, and cell fate determining transcription factors? Approach- As a model system, we use the Drosophila embryonic / larval nerve cord to study sensorimotor circuits. The functions performed by Drosophila sensorimotor circuits are similar to the function performed by other sensorimotor circuits in other organisms. Drosophila larva are unique, however, in the availability of cutting-edge tool, such as: 1. Sophisticated genetics- The expansive molecular genetic tool kit available in flies, allows us to selectively and reproducible manipulate and monitor the activity of neurons, often achieving single cell resolution. These tools also allow us to manipulate gene function in neurons of interest. 2. Genetically-encoded tools to manipulate and monitor neuronal function- Our lab uses high-throughput behavioral assays combined with genetically-encoded optogenetic effectors to manipulate neuronal function. Further because Drosophila larvae are transparent, we use calcium sensors to in intact freely moving animals to monitor neuronal function. 3. Drosophila larval “connectome”- Connectomics is a burgeoning area of neuroscience research likely to transform the entire field. Connectomics seeks to comprehensively map neurons and their interconnections at subcellular resolution. The importance of the Drosophila larval connectome to our work is that it gives us a complete picture of the nervous system at an unprecedented level of detail. Thus, using the Drosophila embryo / larva, we have a unique opportunity to answer fundamental questions with a new level of precision. Our studies are expected to provide insights relevant to nervous system evolution and motile robot design, to produce a detailed understanding of how neural circuits allow animals to move, and to generate developmental insight relevant to stem cell reprogramming that could be used to replace diseased/damaged neural tissue.

Keywords

Drosophila, Motor Activity, Sensory Function, Neuron, Stem Cell, Transcription Factor, Lineage, Cell

Education

Brown University, Providence, RI, BS Biology 06/2008
University of California, San Francisco, CA, PhD Cell Biology 04/2007
University of Oregon, Eugene, OR, Postdoc Neuronal Circuits 07/2015

Biosciences Graduate Program Association

Awards & Honors

1996 - Academic All-Ivy Selection (fencing) Ivy-League
1998 - Sigma Xi Membership Brown University Chapter of Sigma Xi
2000 - 2005 Predoctoral Fellowship Howard Hughes Medical Insitutue
2012 - 2015 Postdoctoral Fellowship American Heart Association

Publications

Wreden CC, Meng JL, Feng W, Chi W, Marshall ZD, Heckscher ES. Temporal Cohorts of Lineage-Related Neurons Perform Analogous Functions in Distinct Sensorimotor Circuits. Curr Biol. 2017 May 22; 27(10):1521-1528.e4. View in: PubMed
Hirono K, Kohwi M, Clark MQ, Heckscher ES, Doe CQ. The Hunchback temporal transcription factor establishes, but is not required to maintain, early-born neuronal identity. Neural Dev. 2017 Jan 31; 12(1):1. View in: PubMed
Sun X, Heckscher ES. Using Linear Agarose Channels to Study Drosophila Larval Crawling Behavior. J Vis Exp. 2016 11 26; (117). View in: PubMed
Clark MQ, McCumsey SJ, Lopez-Darwin S, Heckscher ES, Doe CQ. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs. G3 (Bethesda). 2016 07 07; 6(7):2023-31. View in: PubMed
Heckscher ES, Zarin AA, Faumont S, Clark MQ, Manning L, Fushiki A, Schneider-Mizell CM, Fetter RD, Truman JW, Zwart MF, Landgraf M, Cardona A, Lockery SR, Doe CQ. Even-Skipped(+) Interneurons Are Core Components of a Sensorimotor Circuit that Maintains Left-Right Symmetric Muscle Contraction Amplitude. Neuron. 2015 Oct 21; 88(2):314-29. View in: PubMed
Heckscher ES, Long F, Layden MJ, Chuang CH, Manning L, Richart J, Pearson JC, Crews ST, Peng H, Myers E, Doe CQ. Atlas-builder software and the eNeuro atlas: resources for developmental biology and neuroscience. Development. 2014 Jun; 141(12):2524-32. View in: PubMed
Manning L, Heckscher ES, Purice MD, Roberts J, Bennett AL, Kroll JR, Pollard JL, Strader ME, Lupton JR, Dyukareva AV, Doan PN, Bauer DM, Wilbur AN, Tanner S, Kelly JJ, Lai SL, Tran KD, Kohwi M, Laverty TR, Pearson JC, Crews ST, Rubin GM, Doe CQ. A resource for manipulating gene expression and analyzing cis-regulatory modules in the Drosophila CNS. Cell Rep. 2012 Oct 25; 2(4):1002-13. View in: PubMed
Heckscher ES, Lockery SR, Doe CQ. Characterization of Drosophila larval crawling at the level of organism, segment, and somatic body wall musculature. J Neurosci. 2012 Sep 05; 32(36):12460-71. View in: PubMed
Faumont S, Rondeau G, Thiele TR, Lawton KJ, McCormick KE, Sottile M, Griesbeck O, Heckscher ES, Roberts WM, Doe CQ, Lockery SR. An image-free opto-mechanical system for creating virtual environments and imaging neuronal activity in freely moving Caenorhabditis elegans. PLoS One. 2011; 6(9):e24666. View in: PubMed
Heckscher ES, Fetter RD, Marek KW, Albin SD, Davis GW. NF-kappaB, IkappaB, and IRAK control glutamate receptor density at the Drosophila NMJ. Neuron. 2007 Sep 20; 55(6):859-73. View in: PubMed
Meno C, Gritsman K, Ohishi S, Ohfuji Y, Heckscher E, Mochida K, Shimono A, Kondoh H, Talbot WS, Robertson EJ, Schier AF, Hamada H. Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation. Mol Cell. 1999 Sep; 4(3):287-98. View in: PubMed
Gritsman K, Zhang J, Cheng S, Heckscher E, Talbot WS, Schier AF. The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell. 1999 Apr 02; 97(1):121-32. View in: PubMed