哈佛贝斯以色列女执事医疗中心&哈佛医学院招聘Staff Scientists：应用单细胞基因组学解码大脑功能
We are seeking Staff Scientists interested in using single-cell RNA sequencing to decode brain regions involved in regulating hunger, other homeostatic motivational drives, and physiology. The goal is to use single-cell genomics to create neural “parts lists” for interesting brain regions, develop hypotheses about how these neural “parts” work within circuits to control behavior and physiology, and finally in collaboration with a team of neuroscientists, interrogate these hypotheses using neuron-specific neuroscience technologies.
Ideal candidates will have experience with RNA-seq, facility with statistics and analyses of big data sets, and be interested in neural circuits controlling homeostatic motivational drives and physiology. Basic programming experience, though not strictly required, is preferred. Candidates must have MS or PhD degrees.
Enabling the above-mentioned goals, our group has state-of-the-art expertise in single neuron and single nuclei transcriptomics (Drop-seq, sNuc-seq, etc.), bioinformatic analysis of single-cell datasets to determine a “parts list” for each brain site (see Campbell JN, et al., Nat Neurosci, 2017), rapid CRISPR/Cas9-mediated generation of recombinase driver mice to provide cell-specific experimental access to newly discovered “parts” (i.e. neurons), and finally cell-specific neuroscience techniques including approaches used for:
1) mapping neural circuitry in mice,
2) manipulating neural activity, in vivo, using optical and/or chemogenetic approaches,
3) monitoring of neural activity in vivo withCa2+-based imaging and/or optetrode technologies,
4) brain slice electrophysiology,
5) advanced viral technologies.
Bradford B. Lowell MD, PhD
Professor of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School,
Boston, Massachusetts.
Letters of application and CVs should be emailed to：blowell@bidmc.harvard.edu
Lab website: https://www.lowelllab.com
We utilize genetic engineering techniques in mice, in conjunction with electrophysiology, opto-/chemogenetics, single-cell transcriptomics and rabies mapping, to elucidate central neurocircuits controlling feeding behavior, body weight homeostasis, and fuel metabolism. Specifically, transgenic, knockout, knockin, and cre-dependent AAV viral approaches (for delivery of optogenetic, DREADD and monosynaptic rabies reagents) are used to manipulate and map neuronal circuits. The goal of these studies is to link neurobiologic processes within defined sets of neurons with specific behaviors and physiologic responses. The ultimate goal is to mechanistically understand the “neurocircuit basis” for regulation of food intake, energy expenditure and glucose homeostasis. Given our expertise in gene knockout and transgenic technology, we can efficiently and rapidly create numerous lines of genetically engineered mice, important examples being neuron-specific ires-Cre knockin mice, which enable cre-dependent AAV technology. This allows us to bring novel, powerful approaches to bear on the neural circuits underlying behavior and metabolism. Our combined use of mouse genetic engineering, brain slice electrophysiology, and whole animal physiology is ideally suited to studying these problems.
Recent publications from our collaborative research group:
Campbell JN, Macosko EZ, Fenselau H, Pers TH, Lyubetskaya A, Tenen D, Goldman M, Verstegen AM, Resch JM, McCarroll SA, Rosen ED**, Lowell BB**, Tsai LT**. A molecular census of arcuate hypothalamus and median eminence cell types. Nat Neurosci 20: 484-496, 2017.
Livneh Y, Ramesh RN, Burgess CR, Levandowski KM, Madara JC, Fenselau H, Goldy GJ, Diaz VE, Jikomes N, Resch JM, Lowell BB**, Andermann ML**. Homeostatic circuits selectively gate food cue responses in insular cortex. Nature 546: 611-616, 2017
Fenselau H, Campbell JN, Verstegen AMJ, Madara JC, Xu J, Shah BP, Resch JM, Yang Z, Mandelblat-Cerf Y, Livneh Y and Lowell BB. A rapidly-acting glutamatergic ARCàPVH satiety circuit postsynaptically regulated by a-MSH. Nat Neurosci 20: 42-51, 2017.
Resch JM, Fenselau H, Madara JC*, Wu C, Campbell JN, Lyubetskaya A, Dawes BA, Tsai LT, Li MM, Livneh Y, Ke Q, Kang PM, Fejes-Tóth G, Náray-Fejes-Tóth A, Geerling JC**, Lowell BB**. Aldosterone-sensing neurons in the NTS exhibit state-dependent pacemaker activity and drive sodium appetite via synergy with angiotensin II signaling. Neuron 96, 190–206, 2017.
Mandelblat-Cerf Y, Kim A, Subramanian S, Burgess CR, Tannous BA, Lowell BB**, Andermann ML**. Bidirectional anticipation of future osmotic challenges by vasopressin neurons. Neuron 93: 57-65, 2017
Garfield AS**, Shah BP, Burgess CR, Li MM, Li C, Steger JS, Madara JC, Campbell JN, Kroeger D, Scammell TE, Tannous BA, Myers Jr MG, Andermann**, Krashes MJ**, Lowell BB**. Dynamic GABAergic afferent modulation of AgRP neurons. Nat Neurosci19: 1628-1635, 2016.
Kong D, Dagon Y, Campbell JN, Guo Y, Yang Z, Yi X, Aryal P, Wellenstein K, Kahn BB**, Sabatini BL**, Lowell BB**. A postsynaptic AMPK->p21-activated kinase pathway drives fasting-induced synaptic plasticity in AgRP neurons. Neuron 91: 25-33, 2016.
Garfield AS, Li C, Madara JC, Shah BP, Webber E, Steger JS, Campbell JN, Gavrilova O, Lee CE, Olson DP, Elmquist JK, Tannous BA, Krashes MJ**, Lowell BB**. A neural basis for melanocortin-4 receptor regulated appetite. Nat Neurosci 18: 863-71, 2015.
Mandelblat-Cerf Y, Ramesh RN, Burgess CR, Patella P, Yang Z, Lowell BB, Andermann ML. AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. eLife. 2015;4.
Krashes MJ, Shah BP, Madara JC, Olson DP, Strochlic DE, Garfield AS, Vong L, Pei H, Watabe-Uchida M, Uchida N, Liberles SD, Lowell BB. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature 507: 238-42, 2014.
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