Depending on one's particular field of research, the next step is to send an email to the Principal Investigator with whom one would like to work, in order to present not only one's idea, but also oneself.
Professor and Co-Director Maiken Nedergaard nedergaard@sund.ku.dk
Professor and Co-Director Steven Goldman goldman@sund.ku.dk
Professor Hajime Hirase hirase@sund.ku.dk
Associate Professor Verena Untiet verena@sund.ku.dk
Associate Professor Yuki Mori yuki.mori@sund.ku.dk
Background: Astrocytes are the primary homeostatic cells in the central nervous system (CNS), and one of their critical roles includes the regulation of extracellular ionic composition (ionostasis). Recently, we discovered that astrocytes serve as a dynamic reservoir for chloride (Cl-), significantly modulating inhibitory transmission that depends entirely on this anion. In a series of experiments involving awake, behaving mice, we observed that an increase in intracellular Cl- concentration in astrocytes ([Cl-]i) suppresses neuronal activity, while a decrease in astrocytic [Cl-]i enhances it. We provided evidence that this mechanism is mediated by Cl- efflux through GABAA receptors (GABAAR) expressed on astrocytes. Moreover, we found that astrocytic [Cl-]i is brain state-dependent, maintaining high and stable levels during sleep, and exhibiting dynamic, lower levels during wakefulness. These fluctuations in astrocytic chloride significantly influence the excitation/inhibition balance in both healthy and diseased brains. Next, we will investigate the implications of modulating astrocytic Cl- on sleep architecture and in pathophysiological conditions such as epilepsy.
The position: We are looking for a Master student to complete our team and help us decipher the role of astrocytic Cl- as regulator of E/I balance in sleep architecture or pathophysiological conditions such as epilepsy. We are using a broad spectrum of state-of-the-art imaging and electrophysiology techniques in in vivo mouse experiments.
About the lab: You will be part of a young team, which was founded in Nov 2022. Our lab consists of two Postdocs, and four PhD students. Our group is part of the Center for Translational Neuromedicine, which is part of SUND KU and located at Panum.
Your background: You are a highly motivated student with an interest in how the brain works. You are open and curious, eager to learn new techniques, a team player and interested in becoming a member of a young and dynamic, international team. Pre-requisites are good communications skills in English and a FELASA certificate.
Background: Astrocytes are the primary homeostatic cells in the central nervous system (CNS), and one of their critical roles includes the regulation of extracellular ionic composition (ionostasis). Recently, we discovered that astrocytes serve as a dynamic reservoir for chloride (Cl-), significantly modulating inhibitory transmission that depends entirely on this anion. In a series of experiments involving awake, behaving mice, we observed that an increase in intracellular Cl- concentration in astrocytes ([Cl-]i) suppresses neuronal activity, while a decrease in astrocytic [Cl-]i enhances it. We provided evidence that this mechanism is mediated by Cl- efflux through GABAA receptors (GABAAR) expressed on astrocytes. Moreover, we found that astrocytic [Cl-]i is brain state-dependent, maintaining high and stable levels during sleep, and exhibiting dynamic, lower levels during wakefulness. These fluctuations in astrocytic chloride significantly influence the excitation/inhibition balance in both healthy and diseased brains. Next, we will investigate the implications of modulating astrocytic Cl- on sleep architecture and in pathophysiological conditions such as epilepsy.
The position: We are looking for a Master student to complete our team and help us decipher the role of astrocytic Cl- as regulator of E/I balance in sleep architecture or pathophysiological conditions such as epilepsy. We are using a broad spectrum of state-of-the-art imaging and electrophysiology techniques in in vivo mouse experiments.
About the lab: You will be part of a young team, which was founded in Nov 2022. Our lab consists of a Postdoc, two PhD students and a research assistant. Our group is part of the Center for Translational Neuromedicine, which is part of SUND KU and located at Panum.
Your background: You are a highly motivated student with an interest in how the brain works. You are open and curious, eager to learn new techniques, a team player and interested in becoming a member of a young and dynamic, international team. Pre-requisites are good communications skills in English and a FELASA certificate.
Supervisors:
Relevant Literature:
Untiet V, Verkhratsky A (2024) How astrocytic chloride modulates brain states. Bioessays DOI: 10.1002/bies.202400004
Untiet V, Nedergaard M, Verkhratsky A (2024) Astrocyte chloride, excitatory-inhibitory balance and epilepsy. Neural Regen Res DOI: 10.4103/1673-5374.390981
Untiet V (2024) Astrocytic chloride regulates brain function in health and disease. Cell Ca DOI: 10.1016/j.ceca.2024.102855
Untiet et al. (2023) Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice. Nat Commun DOI: 0.1038/s41467-023-37433-9
Does this sound interesting to you? Just send an email to verena@sund.ku.dk and we schedule an informal meeting.
In 2019, the two top leading causes of mortality in Denmark were ischemic heart disease and stroke. Yet, treatments for these diseases are limited and reliant upon fast intervention. Understanding the pathogenesis of these diseases may help develop new targets for therapeutics. Interestingly, in both the brain and heart the pathogenesis of ischemic injury changes based on time-of-day.
Stroke and ischemic cardiac events are most severe in the late night. This pattern is not limited to the heart, and the brain-ischemic events are also more severe at the end of the night in the liver. We hypothesize that there is an intrinsic, conserved timing mechanism that may govern ischemic injury in the brain and body. In most mammals, daily changes in gene transcription, physiology, and behavior are controlled by the circadian (~24h) molecular clock, a transcription-translation feedback loop present in almost all cells within the body. Preliminary data suggests that ischemic events in both the brain and heart are more likely to occur when the molecular clock protein BMAL1 is low.
There are two driving questions of this master’s project: 1) does ischemic injury and pathogenesis have the same daily profile across all tissue within the body, and 2) how does the molecular clock contribute to ischemic injury? This project will utilize circadian mutant and other transgenic mouse lines, macroscopic and 2-photon imaging of lymphatic and glymphatic function, and immunohistochemistry to address these questions.
The project will take place in the Center for Translational Neuromedicine (CTN) at the University of Copenhagen and the University of Rochester Medical Center. CTN is an international research group of more than 50 people, with collaborations that span the globe, providing exposure to a wide array of scientific question centered around glial cells. CTN features state-of-the-art facilities and equipment, joint weekly journal clubs and focus groups between Copenhagen and Rochester, and integrative training among undergraduates, graduate students, postdocs and faculty. By integrating international teams and training levels, trainees are exposed to all levels of science from benchwork to science writing to project development.
This project is a collaboration between Dr. Lauren Hablitz, an expert in circadian biology and glymphatic function, and Dr. Maiken Nedergaard, an expert in glial biology, stroke, and discoverer of the glymphatic system. As such, this project will involve research done in Rochester, New York, USA. The lab language is English, and international as well as Danish students are welcome.
Please send your application including a short CV and a short letter of motivation to Dr. Hablitz or Dr. Nedergaard. Lauren Hablitz, PhD Assistant Professor
Department of Neurology Center for Translational Neuromedicine University of Rochester Medical Center
lauren_hablitz@urmc.rochester.edu
https://www.urmc.rochester.edu/labs/hablitz.aspx
Maiken Nedergaard, MD, DMScProfessor
Center for Translational Neuromedicine
University of Copenhagen
https://ctn.ku.dk/research/nedergaard_laboratory
The glymphatic system is responsible for clearing toxic metabolites from the brain during sleep. This network of perivascular spaces lined by astrocytic end feet enables the bulk fluid movement of cerebrospinal fluid into, and interstitial fluid through the brain. Decreased glymphatic function, and thus decreased clearance of waste, has been associated with age, Alzheimer’s disease, diabetes, hypertension, traumatic brain injury, chronic high ethanol intake, chronic unpredictable stress, bacterial meningitis, and, preliminarily, pain.
The majority of these conditions that exhibit glymphatic dysfunction are also associated with increased neuroinflammation characterized in part by increased inflammatory cytokines and reactive gliosis. The main goal of this master’s proposal is to understand how neuroinflammation may alter the structure of the glymphatic system, either in the perivascular or interstitial space, leading to a reduction in flow. This project will involve a combination of live-animal surgery, ex vivo and in vivo imaging, in vivo microdialysis, immunohistochemistry and more.
This project has a special emphasis on chronic pain, a debilitating condition with no effective, non-addictive treatment. We use two pre-clinical models of chronic neuropathic pain: sparse nerve injury and spinal chord injury. Our goal is to understand glymphatic dysfunction in chronic pain, and potentially develop therapeutics to increase glymphatic flow after development of neuroinflammatory pathology.
The project will take place in the Center for Translational Neuromedicine (CTN) at the University of Copenhagen and the University of Rochester Medical Center. CTN is an international research group of more than 50 people, with collaborations that span the globe, providing exposure to a wide array of scientific questions centered around glial cells. CTN features state-of-the-art facilities and equipment, joint weekly journal clubs and focus groups between Copenhagen and Rochester, and integrative training among undergraduates, graduate students, postdocs and faculty. By integrating international teams and training levels, trainees are exposed to all levels of science from benchwork to science writing to project development.
This project is a collaboration between Dr. Lauren Hablitz, an expert in glymphatic function, and Dr. Maiken Nedergaard, an expert in glial biology, pain, and discoverer of the glymphatic system. As such, this project will involve research done in Rochester, New York, USA. The lab language is English, and international as well as Danish students are welcome.
Please send your application including a short CV and a short letter of motivation to Dr. Hablitz or Dr. Nedergaard.
Lauren Hablitz, PhD
Assistant Professor
Department of Neurology
Center for Translational Neuromedicine
University of Rochester Medical Center
lauren_hablitz@urmc.rochester.edu
https://www.urmc.rochester.edu/labs/hablitz.aspx
Maiken Nedergaard, MD, DMSc
Professor
Center for Translational Neuromedicine
University of Copenhagen
nedergaard@sund.ku.dk
https://ctn.ku.dk/research/nedergaard_laboratory/
Migraine affects up to 1 out of 10 and is characterized by a unilateral throbbing headache which can be followed by nausea, vomiting, photo and phonophobia, and exacerbation of headache during physical activity. In about one third of migraine patients, the migraine headache is preceded by transient neurological symptoms lasting 5-60 minutes.
In a recent publication, we have identified several new molecules that likely provoke migraine (see Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model). To test whether inhibiting the signaling of these molecules prevents or aborts migraine headache, we are developing a behavioral assay.
Headache disease models are notoriously tricky to characterize in animal models, since specific biomarkers are lacking, and behavioral assays are only somewhat able to detect the subtle changes migraine attacks might inflict. Just think about how in humans, migraine diagnostics is 100% based on a patient interview, and therefore in clinical settings based on the patient’s subjective experience. This is of course impossible to do in a rodent model.
However, the technological and computational advancement in science has started to change this. We are planning to use tools such as optogenetics, fiber photometry and behavioral sequencing (e.g., Deep Lab Cut) to generate a behavioral assay for migraine with aura in mice where the effect of putative migraine abortive and preventive drugs can be tested.
We are seeking a master student with an interest in translational neuroscience to develop an animal preparation where we use transgene mice to induce migraine with aura using optogenetics, and where we quantify migraine attacks with genetically encoded calcium indicators. All this is to be done in a freely moving awake animal.
About the candidate:
Preferably you have experience with small animal handling, and if you already have FELASA certification that is a plus. The candidate will be trained in transgenic models, optogenetics, fiber photometry and behavioral sequencing. Any prior experience in any of these fields is an advantage for the candidate.
Contact:
Please write an email with your letter of interest and including a 1-page CV to post doc Martin Kaag Rasmussen, Center for Translational Neuromedicine at martin.rasmussen@sund.ku.dk.
Project:
Are you interested in playing a major role in deciphering:
If you are curious to learn and answer these important questions in your thesis project this is the project for you!
Why is it important to study Amyotrophic lateral sclerosis (ALS)?
Amyotrophic lateral sclerosis (ALS) is an incurable condition, characterized by degeneration of upper motor neurons (in the brain) and lower motor neurons (in the brainstem and spinal cord) leading to weaker muscles, paralysis and eventually death within 2-5 years. According to Lancet Neurology study, about 3.4 billion individuals were living with neurological conditions worldwide equating to 43.1% global population (Steinmetz et al, 2021) of which, over 331,000 individuals were suffering from ALS (Vos et al, 2017). Even though major symptoms of ALS constitute motor dysfunction, up to 50% patients develop cognitive impairment, 13% develop frontotemporal dementia (FTD) and the most common mutation occurs in superoxide dismutase (SOD1) gene. Riluzole is the only effective and clinically used drugs globally to reduce glutamate mediated excitotoxicity and thus prolongs lifespan to approximately 3 months. However, the drug comes with side-effects which further compromises the quality of life of ALS individuals.
What are we lacking in order to find an appropriate treatment for ALS?To find an effective treatment for ALS, we first need to understand what is happening to the neurons and glial cells at network level before the onset of disease and during the disease progression in the brain as well as the spinal cord. Revealing the progression of the disease at neuroglial network level with help understanding its complex mechanism.
Here you will use an SOD1 mouse model of ALS. These mice carry mutations in the SOD1 gene which causes motor neuron degeneration and mimic various aspects of ALS in humans. You will use in vivo imaging (such as fiber photometry and 2-photon imaging) and in vitro assays to reveal the mechanistic changes at neuroglial network level in ALS.
Candidate: You are a motivated student with an interest in neurodegenerative diseases and interest in how the brain as well as the spinal cord work. You are curious to learn new skills and a team player. You are required to have a Felasa certificate and can communicate in English.
Contact: Send your CV to Jaspreet Kaur Daniil, Assistant Professor at Center for Translational Neuromedicine, email: jaspreet.kaur@sund.ku.dk
