Students with a keen interest in neuroscience are invited to apply for one of 6 vacant doctoral studentships within the newly established PhD program CavX – Calcium channels in excitable cells.In the PhD program, which is run by the Innsbruck’s Universities and financed by the Austrian Science Fund (FWF), we are studying the roles of voltage-gated calcium channels (Cav) in health and disease. Students accepted into the program will be enrolled in the existing graduate program in Neuroscience and receive a specialized training in signaling processes of ion channels, membrane excitability, calcium signaling, and channelopathies.Research topics: Roles of voltage-gated calcium channels in CNS neurons, skeletal muscle and pancreas, brain disorders, retinal dysfunction, and diabetes.Candidates must hold a master's degree or equivalent in the life sciences, medicine, pharmacy or physics. Excellent command of English is indispensable. >>> Dowload files: Call and project descriptions / Application form <<< Applications must be received by May 28th 2018! The top candidates will be interviewed in Innsbruck in July 2018. Research will start in October 2018.Please scroll down for information onResearch projectsProject descriptionsGeneral informationApplication Research projectsCharacterization of the interactions established by STAC3 in skeletal muscle (Campiglio) - position is already filled!Structure and function of calcium channel splice variants in muscle (Flucher)Calcium channels in congenital stationary night blindness (Koschak)Voltage-gated calcium channels and synaptic functions (Obermair) - position is already filled!Voltage-gated calcium channel signaling in brain disorders (Striessnig) - position is already filled!Role of voltage gated calcium channels in pancreatic hormone release (Tuluc)CavX-associated research projects7. Calcium channels in intra-islet cell communication (Meyer) Project descriptions Project 1: Characterization of the interactions established by STAC3 in skeletal muscleN.B. This position is already filled!Skeletal muscle excitation-contraction (EC) coupling relies on the functional coupling of the voltage sensor (Cav1.1) and of the calcium release channel (RyR1). However, the precise mechanism of signal transmission during EC coupling between Cav1.1 and RyR1 remains elusive. Recently an adaptor protein, STAC3, was identified as essential for EC coupling. Ongoing work in our laboratory identified two interactions between STAC3 and Cav1.1 and an additional putative interaction between STAC3 and the RyR1. The goal of the PhD thesis project is to characterize the interactions STAC3 establishes within the EC coupling complex and their role in EC coupling.Methods: Molecular biology, cell culture, primary zebrafish cultures, high- and super-resolution fluorescent microscopy, FRAP, patch-clamp and calcium imaging.References: Campiglio et al. (2018) J Cell Physiol, under review; Campiglio et al. (2018) PNAS USA 115(6):1376-1381; Wong King Yuen et al. (2017) PNAS USA 114(45):E9520-E9528; Campiglio & Flucher (2017) Sci Rep. 7:41003.Project leader: Dr. Marta Campiglio Project 2: Structure and function of calcium channel splice variants in muscleIn skeletal muscle voltage-gated calcium channels control contraction and regulate multiple developmental processes including fiber type specification and neuro-muscular junction development. Alternative splicing results in Cav1.1 channel variants with distinct current properties and physiological roles. Recent structure analysis and ongoing molecular dynamics simulation provides mechanistic models explaining how specific gating properties are caused. The goal of this PhD thesis project is to experimentally examine the predictions of these structure-function models by a combined mutagenesis and electrophysiology approach.Methods: Site-directed mutagenesis of recombinant Cav1.1 channels; expression in heterologous cell systems and functional reconstitution of null-mutant muscle cells; functional analysis with whole-cell and single-channel patch-clamp recordings and with microfluorometry analysis using fluorescent calcium indicators.References: Tuluc et al., 2015, Structure, 24:261-271; Tuluc et al., 2016 J. Gen. Physiology, 147:437-449; Flucher and Tuluc 2017, J. Physiol., 595:1451-1463; Campiglio and Flucher, 2017, Sci. Rep., 7:41003; Campiglio et al., 2018, PNAS, 115:1367-1381.Project leader: Ao.Univ.-Prof. Dr. Bernhard E. Flucher Project 3: Calcium channels in congenital stationary night blindnessPhotoreceptors are morphologically and physiological highly specialised light sensing cells of the retina where sustained release of glutamate from ribbon synapses is calcium dependent and L-type calcium channels (LTCC) serve as the predominant source for Ca2+ entry. Mutations in the CACNA1F gene encoding Cav1.4 LTCCs were identified among patients diagnosed with congenital night blindness type 2 (OMIM: 30071). Ongoing work investigates the important role of Cav1.4 channels as calcium source for neurotransmitter release and stabilizers of the retinal synapse. The aim of this PhD project is to further test also the pharmaco-therapeutic potential of retinal LTCCs. Methods: Retinal morphology and synapse structure (high-resolution fluorescent and electron microscopy; dye filling); functional analyses in retinal whole-mounts and slices (patch-clamp, slice electrophysiology; multielectrode array analyses); cell culture; retinal AAV gene-therapy References: Knoflach et al. (2015) Channels (Austin) 9(5):298-306; Bacchi et al. (2015) IOVS 56(8):4846-56.; Seitter and Koschak (2018) Neuropharmacology 132:58-70. (Review); Pangrsic et al. (2018) Physiol Reviews (Review).Project leader: Ao. Univ. Prof. Alexandra Koschak Project 4: Voltage-gated calcium channels and synaptic functionsN.B. This position is already filled! In the central nervous system voltage-activated calcium channels regulate calcium influx and mediate cell-cell signaling functions. Altered function of α1 or α2δ subunits has been implicated in CNS diseases such as epilepsy, Parkinson, and mood disorders. Ongoing work in our laboratory provided novel insights into the role of specific subunits of pre- and postsynaptic calcium channels role in channel localization and glutamatergic and GABAergic synaptic transmission. The goal of the PhD thesis project is to understand how specific calcium channel subunit isoforms and splice variants regulate synaptic differentiation and how they contribute to aberrant synaptic functions and neuropsychiatric disorders.Methods: Synapse structure/function analyses; experimental cell culture models; cell culture, high- and super-resolution fluorescent microscopy, histology, patch-clamp and slice electrophysiology, electron microscopy.References: Fell et al. (2016) J Neurosci. 36:11024-11036; Stanika et al. (2016) Sci Rep. 6:34528; Stanika et al. (2015) Curr Mol Pharmacol. 8):95-101. (Review); Geisler et al. (2015) Gen Physiol Biophys. 34:105-118. (Review)Project leader: Assoz.-Prof. (PD) Mag. Dr. Gerald J. Obermair Project 5: Voltage-gated calcium channel signaling in brain disordersN.B. This position is already filled! Voltage-activated calcium channels regulate the activity-dependent calcium influx into electrically excitable cells allowing fine-tuning of calcium-dependent signaling events and of electrical excitability. We investigate the role of voltage-gated Ca2+-channels for human disease, in particular of L-type calcium channels (LTCCs). We have recently shown that gain-of-function mutations in the pore-forming subunit of an LTCC confer a strong risk for autism spectrum disorders with and without other neurological manifestations. Goal of the PhD thesis is to understand how altered channel function affects cellular signaling and leads to abnormal neuronal development and function. For these studies a suitable mouse model has already been generated.Methods: Heterologous expression of calcium channel complexes in neurons; cell culture, patch-clamp and slice electrophysiology, gene expression profiling; protein biochemistry, immunohistochemistry, animal behavioral analysisReferences: Pinggera et al. (2015) Biol Psychiatry 77:816-822; Pinggera et al. (2017) Hum Mol Genetics 26:2923-2932; Azizan et al (2013) Nat Genetics 45:1055-1060; Baig et al. (2011) Nat Neurosci 14:77-84; Pinggera and Striessnig (2016) 594:5839-5849 (Review).Project leader: Univ.-Prof. Dr. Jörg Striessnig Project 6: Role of voltage gated calcium channels in pancreatic hormone release Hormone synthesis and release from pancreatic islet cells is determined by the activity of several high-voltage gated calcium channels isoforms. Previously we have shown that genetic deletion of the α2δ-1 calcium channel subunit leads to diabetes in mice in a sex specific manner (Mastrolia et al. 2017, Diabetes). The goal of the current PhD thesis project is to identify the role of other calcium channel subunits loss-of function or gain-of function on pancreatic hormone release and β-cell survival. To this end, the successful PhD candidate will have the opportunity to utilize several knock-out or knock-in mouse models already present in the host laboratory or available through local collaborations. The lab welcomes outstanding international students with a Masters degree in life sciences, with a passion for research. Methods: The project will involve a wide range of methods including electrophysiology (voltage clamp, current clamp, capacitance measurements), calcium imaging, super resolution fluorescent microscopy, histology, single cell RNA-seq, ELISA. References: Mastrolia et al. (2017) Diabetes, 10.2337/db16-0336; Azizan et al. (2013) Nat. Genet. 10.1038/ng.2716; Barg et al. (2001) Biophys. J., 0006-3495/01/12/3308/16.Project leader: Petronel Tuluc, PhD Project 7: Calcium channels in intra-islet cell communication L-type calcium channels (LTCC) are crucial in controlling β-cell insulin synthesis and secretion, electrical activity, and β-cell mass. Recently, using zebrafish as a model to study diabetes risk factors, we showed that genetic loss of the α1C subunit gene CACNA1C causes unsynchronized and glucose-independent β-cell excitation in combination with hyperglycemia. The goal of the PhD thesis project is to understand how altered channel function affects islet synchronized hormone release and paracrine modulation by combining genetic and in vivo calcium imaging approaches. For this project several calcium channel mutants and strains expressing different genetically encoded calcium indicators have already been generated. Methods: Molecular genetics, CRISPR/CAS9 genome editing, high resolution in vivo and ex vivo calcium imaging, single cell and whole islet patch-clamp, histology, electron microscopy References: Kimmel et al. (2015) Sci. Rep. 5, 14241; Schmitner et al. (2017) Dis Model Mech. 10: 307-321; Freudenblum et al. (2018) Development 145, dev158477; Kimmel and Meyer (2016) Meth Cell Biol. 134: 431-461 (Review) Salary: According to the rates of the ‘Kollektivvertrag’ for PhD students plus travel funds for international scientific meetings. Contact: Univ. Prof. Dr. Dirk Meyer, University of Innsbruck, Institute of Molecular Biology, Technikerstr. 25, A-6020 Innsbruck, Austria. Email: email@example.com Phone: +43-(0)512-507-51410 General information 1. Program descriptionVoltage-gated calcium channels (Cav) are critical regulators of vitally important cellular functions ranging from muscle contraction to brain functions such as learning and memory. Given their manifold roles it is not surprising that calcium channels are linked to a growing number of human diseases. Hence understanding the structural complexity, composition, and molecular interactions of calcium channels is key for elucidating their roles in physiological functions and ultimately in disease.In the CavX PhD program we combine the worldwide unique research focus on Cavs in Innsbruck with an excellent doctoral training in Neuroscience. To this end CavX builds on the excellent scientific and methodological expertise of the steadily growing Cav faculty in Innsbruck, which consist of a lively mixture of experienced and newly established research groups (Campiglio, Flucher, Koschak, Obermair, Striessnig, Tuluc). Thus CavX combines a strong scientific focus on calcium signaling in excitable cells in general and the role of Cavs in physiology and human disease in particular with a sound education in neuroscience. Scientifically CavX comprises projects on the structure-function relationships, specialized functions in vision and in hormone secretion, synaptic modulation and connectivity in brain disorders, as well as skeletal muscle function. These research topics are highly relevant for the pathophysiology and treatment of a variety of diseases including brain disorders (e.g. autism, anxiety), diabetes, night blindness, and myopathies.CavX utilizes state-of-the-art methodologies including newly developed cell culture models, unique genetically modified mice, super-resolution microscopy, electrophysiology and mouse behavior (Singewald), zebrafish technology (Grabner), and molecular modeling and dynamics (Liedl). All faculty members have a strong history of collaboration and PhD student training. This is evidenced by many joint publications, meetings, and joint research grants (e.g. SFB F44). The program also achieves high international visibility, e.g. by organizing the European Calcium Channel Conferences every three years, which brings the world leaders of the field to Innsbruck.CavX students will be offered a variety of networking opportunities and thereby connect with the other students. CavX faculty will contribute expertise and novel state-of-the-art methodology to the entire Neuroscience program. These intensified interactions will fill an important niche, namely the education of cellular and molecular neuroscientists with a particular focus on cellular physiology. This focus is of increasing international importance, particular for the identification of new drug targets for the future treatment of diseases for which current therapeutic approaches are insufficient (e.g. autism). 2. RequirementsCandidates must hold a master's degree or equivalent in the life sciences, medicine, pharmacy or physics. Excellent command of English is indispensable. Accepted PhD students will be hosted at the PIs institutions at the Medical University of Innsbruck or at the University of Innsbruck.The PhD student salary is according to the rates of the Austrian Science Fund (FWF) for PhD students plus travel funds for international scientific meetings (link).Applications must be received by September 10th 2018!The top candidates will be interviewed in Innsbruck . Research will start in October 2018. Application PhD candidates need to fill out the application form and submit the signed application form by E-mail to CavX.Office@gmail.com. Applications must be received by September 10th 2018!