Ruprecht-Karls-Universität Heidelberg
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SFB 1158_Kuner_Simonetti0119 - Scientist (f/m) / PhD position
Project no:
SFB 1158_Kuner_Simonetti0119

Project leader:

Project supervisor:
Kuner, Rohini
Application deadline:
15. Aug 2019
Start of PhD project:
1. Oct 2019

Project description:

Title:
Neuron-Glia interaction in chronic pain: characterization of cell type-specific transmitter release and their downstream signaling
Summary:
Many form of chronic pain, that are poorly responding to common therapies, can be treated with antidepressants, but the mechanism is unknown. Furthermore, in chronic pain conditions, microglia and astrocytes become reactive and exhibit dysregulated Ca2+ signaling, which in turn might lead to increased or decreased gliotransmitter release. The central question of this project is to understand if and how glia cells are mediating the analgesic effect of antidepressants. In particular, we aim to identify molecules released specifically by astrocytes and microglia in basal and neuropathic state, characterize the signaling pathways that will be activated and their modulation in presence of antidepressant.
We will address this question studying astrocytes and microglia structural and functional dynamics in neuropathic pain conditions in mice in brain as well as in spinal cord. We will use genetic, viral and pharmacologic tools to modulate glia signaling specifically in one cell types in vivo and test behavioral effects as read outs.
References:
Paldy E, Simonetti M, Worzfeld T, Bali KK, Vicuña L, Offermanns S, Kuner R. Semaphorin 4C Plexin-B2 signaling in peripheral sensory neurons is pronociceptive in a model of inflammatory pain. Nat Commun. 2017 Aug 2;8(1):176.

Agarwal A, Wu PH, Hughes EG, Fukaya M, Tischfield MA, Langseth AJ, Wirtz D, Bergles DE. Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. Neuron. 2017 Feb 8;93(3):587-605.e7

Vicuña L, Strochlic DE, Latremoliere A, Bali KK, Simonetti M, Husainie D, Prokosch S, Riva P, Griffin RS, Njoo C, Gehrig S, Mall MA, Arnold B, Devor M, Woolf CJ, Liberles SD, Costigan M, Kuner R. The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell–derived leukocyte elastase. Nat. Med. 2015;21:518–523.

Simonetti M, Agarwal N, Stösser S, Bali KK, Karaulanov E, Kamble R, Pospisilova B, Kurejova M, Birchmeier W, Niehrs C, Heppenstall P, Kuner R. Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways. Neuron 2014;83:104–121.

Simonetti M, Hagenston AM, Vardeh D, Freitag HE, Mauceri D, Lu J, Satagopam VP, Schneider R, Costigan M, Bading H, Kuner R. Nuclear Calcium Signaling in Spinal Neurons Drives a Genomic Program Required for Persistent Inflammatory Pain. Neuron 2013;77:43–57.
Methods that will be used:
Standard molecular biology techniques, protein biochemistry, immunohistochemistry, quantitative confocal microscopy, in vivo 2 Photon microscopy, Calcium imaging, neuronal and glial primary cell culture, in vivo mouse work, rodent behavioral pain assessments.
Cooperation partners:
Members of Heidelberg Pain Consortium SFB1158. In particular, the PhD candidate will strongly collaborate with the group of Dr. Amit Agarwal (UniHD) and Prof. Frank Kirchhoff (Uni Saarland) in the frame of the SFB 1158 project A09N. The recruited student will be part of the group of Prof. Rohini Kuner working directly with Dr. Manuela Simonetti.
Personal qualifications:
We are looking for a highly motivated and enthusiastic PhD candidate. Applicants should hold a diploma/Masters in a biomedical, Life science (i.e. M.S. in Biology, Biochemistry, Neurobiology, Neuscience, Medicine) or related disciplines. Strong analytical and technical skills as well as ability to work in a team and independently plan and conduct experimental research are essential. Furthermore, the candidate should demonstrate a problem-solving, proactive attitude. A background and hands-on laboratory experience in molecular cell biology and biochemistry as well as animal handling experience will be strongly preferred. Since we provide an international working environment, good English language skills are required (no German language requirement)
Keywords:
mouse pain behavior, neuron-glia comunication, cell signaling, calcium imaging, in vivo 2P microscopy