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SynAGE is seeking
13 highly motivated PhD candidates
Requirements profile:
- completed university degree (MSc or comparable) in neuroscience, biology, biochemistry, psychology or related disciplines
- a strong motivation to learn new methodologies and the ability to independently plan, conduct and analyse experiments
- enthusiasm and dedication for basic and translational research
- creative and active team players, fluent in English
Your benefits:
- You have the opportunity to pursue a PhD and are supported and promoted accordingly
- You will be working in an interdisciplinary environment and an international team
- You have the opportunity to learn cutting-edge neuroscience and neurotechniques
- You can expect excellent infrastructure, modern workspaces and very well-equipped labs
- You will experience strong mentoring, professionalism training and career support
The PhD candidates will work on the following topics:
A1: Regulation of mechanosensitive signaling by neural extracellular matrix
This project, co-directed by Prof. A. Dityatev (DZNE Magdeburg) and Prof. C. Seidenbecher (LIN), aims to identify key components of neural extracellular matrix, which regulate the activation of mechanosensitive channels and downstream signaling, and target them genetically and pharmacologically to restore functional and structural synaptic plasticity in aged mice. Biochemical, molecular biological, imaging and electrophysiological methods will be used in this study.
The PhD candidate will work at the Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE).
A2: The healthy ageing synapse: Roles of the hippo kinase Ndr2
Previous work in this project has shown that loss of Ndr2 in mice protects them from ageing related changes in neuronal gene expression, neuroinflammation, and loss of hippocampus dependent cognitive functions. In this PhD project we want to unravel the molecular and cellular mechanisms of by which Ndr2 is involved in ageing of neuronal cells. To this end, in cell culture experiments and life-cell imaging we will investigate the molecular and cellular changes including gene expression, cytoskeletal reorganization, and growth of neurites and dendrites upon acute and chronic activation and inactivation of Ndr2 kinase. Our observations will be translated in vivo using conditional transgenic and knock out mice.
The PhD candidate will work at the Faculty for Natural Sciences of the Otto von Guericke-University Magdeburg (OvGU).
A3: Rejuvenating astrocytic influences on tripartite synapse function with anti-aging drugs
As part of project A3, we will aim to revert age-related alterations of astrocytic mechanotransduction by targeting the Hippo pathway as one of the relevant signaling hubs conveying mechanical forces. We will test anti-aging drugs and use genetic targeting strategies in combination with biochemical, cell and molecular biology and imaging techniques to evaluate effects on astrocytic physiology and their contribution to synaptic function.
The PhD candidate will work at the Medical Faculty of the Otto von Guericke-University Magdeburg (OvGU).
B1: Towards new treatments for vascular dementia
This project, directed by Prof. A. Dityatev (DZNE Magdeburg) in close collaboration with Prof. S. Schreiber (OvGU), aims to elucidate inflammatory processes in the neurovascular unit during aging and target sodium-glucose cotransporters, extracellular proteolysis and the complement system to improve blood-brain-barrier function and interfere with synaptic elimination and other forms of synaptic remodeling induced by microglia near to microvascular damage sites in mice.
The PhD candidate will work at the Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE).
B2: Towards new treatments for vascular dementia – translational part
This project, directed by Prof. S. Schreiber (OvGU Magdeburg) in close collaboration with Prof. A. Dityatev (DZNE), focuses on brain microvascular plasticity in humans. It aims to investigate microvascular hemodynamics, inflammatory processes and blood-brain barrier function in relation to neural network connectivity during aging and physical stress, and how these relationships can be improved by different pharmacological therapies.
The PhD candidate will work at the Medical Faculty of the Otto von Guericke-University Magdeburg (OvGU).
C1: The synaptic proteome in high-risk ageing
Synaptic insulin resistance underlies cognitive impairment in obesity and is a major risk factor for Alzheimers‘ Disease. In a mouse model of high-risk ageing we try to prevent cognitive decline by targeting nodal points of synaptic function that are dysregulated in disease. Advanced proteomic methods will be combined with functional analysis encompassing work in primary neuronal cultures and in vivo.
The PhD candidate will work at the Leibniz Institute for Neurobiology (LIN).
C2: tba
description follows
The PhD candidate will work at the Leibniz Institute for Neurobiology (LIN).
C3: tba
description follows.
The PhD candidate will work at the Medical Faculty of the Otto von Guericke-University Magdeburg (OvGU).
D1: Functional network changes of the hippocampal-posterior cortical memory network in ageing
The Phd student will investigate functional network changes in the hippocampus and connected posterior cortex that occur with ageing and in the presence of early Alzheimer’s pathology. He/she will analyze functional MRI data including resting-state and task fMRI/connectivity data to assess hyperactivity and network changes in ageing along with associated memory deficits in humans. The PhD student will assess critical tipping points on the path towards pathological ageing by incorporating biomarkers of Aβ/tau pathology. The PhD project will closely interact with the corresponding MD project, including the translation of findings across species.
The PhD candidate will work at the Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE).
D2: Memory function and network dynamics in hippocampal-cortical circuits
The PhD student will investigate patterns of hyperactivity that occur with aging and lead to altered long-range and local synaptic function and subsequent aberrant network excitability along with associated memory deficits. Specifically, the candidate will investigate the underlying contribution of cell-type specific projections within hippocampal-cortical circuits in mice and characterize the synaptic changes within long-range versus local cortical circuits across aging. The candidate will gain valuable experience with in vivo two-photon imaging, molecular cell identification, and computational analysis.
The PhD candidate will work at the Leibniz Institute for Neurobiology (LIN) with Prof. Janelle Pakan and in close cooperation with Prof. Stefan Remy (LIN), as well as Dr. Anne Maass (DZNE Magdeburg), where the results will also be directly related to MRI-based experiments in humans.
E1: Muscarinic signaling in the hippocampus and its relevance for cognitive vitality in old age
Based on extensive molecular analysis of muscarinic signaling we will target defined synaptic connections in hippocampal microcircuits with a known role for a given cognitive faculty that can be tested in behavioural paradigms (working memory as well as pattern separation/completion) and associated in vivo network activity changes. The ultemate aim is to boost detoriating synaptic function in old age. The methodology encompasses molecular, cellular, circuit and behavioral approaches with cutting edge technology (i.e. Super-Resolution microscopy, multi-electrode electrophysiological recordings, spatial transcriptomice etc,).
The PhD candidate will work at the Leibniz Institute for Neurobiology (LIN).
E2: Cholinergic mechanisms controlling local circuits in the dentate gyrus
Prior work in our group has demonstrated a critical role of cholinergic neuromodulation in the control of hippocampal circuit activity, plasticity and engram formation, and the detrimental effects of its ageing related decline. In this project, we will investigate with electrophysiological tools in vitro and in vivo, chemo- and pharmacogenetic intervention the cholinergic modulation network activity in the hippocampus. We will examine the effect of modulating afferences from the medial septum and the role of specific local interneuron populations in generating behaviorally relevant network activity patterns, and the formation of memory engrams.
The PhD candidate will work at the Faculty for Natural Sciences of the Otto von Guericke-University Magdeburg (OvGU).
E3: Cholinergic modulation of cingulo-hippocampal interactions in humans
The project addresses functional and neurochemical interactions of performance monitoring and memory systems in humans using EEG, fMRI, and pharmacological challenges and focuses on cholinergic interactions via the M1 receptor. Double-blind placebo-controlled studies with cholinergic antagonists and agonists will be carried out in healthy young and older participants, while they perform cognitive tasks and neural data will be collected non-invasively. Computational learning models will be fit to the participants‘ behavior and inform analysis of the neural data. The candidate should have a master’s degree in psychology, medicine, neuro- or cognitive sciences or a neighboring field. Experience with cognitive neuroscience, neuroimaging, and/or programming is advantageous. The PhD candidate will work at the Faculty for Natural Sciences of the Otto von Guericke-University Magdeburg (OvGU).
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