Despite a high level of metabolic activity, the brain does not have a conventional lymphatic system to remove metabolites. The glia-lymphatic (glymphatic) system is a waste removal system that uses the perivascular space of the brain for fluid transport. The glymphatic system is a bulk flow system driven arterial pulsation and results in convective flow in the perivascular spaces. The glymphatic system is most active in the sleep state, where production of cerebrospinal fluid (CSF) is highest and the interstitial space is larger. Solutes as well as peptides such as amyloid beta can be transported in perivascular pathways by the glymphatic system and eliminated to the lymphatic vessels. Accumulation of proteins, such as amyloid beta, is a common feature of neurodegenerative diseases and we believe that the control of the glymphatic system could prevent or curb neurodegenerative diseases. Due to the recent discovery of the glymphatic system, many new discoveries are waiting to be made, including how to effectively manipulate the glymphatic system.
Astrocytes are the key regulators of brain homeostasis. Their endfeet processes ensheath the cerebral vasculature and contact thousands of synapses. We are interested in the endfeet of astrocytes, as they form perivascular pathways used by the glymphatic system for fluid transport. Aquaporin 4 (AQP4) water channels in the astrocyte endfeet are crucial for influx of cerebrospinal fluid (CSF) into the brain and clearance of solutes. Besides AQP4 molecular drivers of glymphatic flow remain elusive.
Similar to the lymphatic system, the glymphatic system connects to lymph nodes in the cervical region. Thus, there is a strong association between glymphatic and immune function. Fluid drains from the brain into meningeal lymphatic vessels, to the nasal mucosa via the cribriform plate, via spinal and cranial nerves, or simply perivenously. Drainage from the brain will mount an immune response in cervical lymph nodes. The idea of the brain being ‘immune privileged’ remains true in the sense that there are much fewer patrolling T cells in the brain e.g. than in the skin. However, meningeal lymphatic vessels and CSF efflux to cervical lymph via the nasal mucosa is understudied in relation to central nervous system immune function.
Principal investigator, Dr. Iben Lundgaard, is recipient of a large Wallenberg Foundation starting grant. Over the next 4 years, this grant covers 2 PhD students, 2 postdocs plus technical support and also includes running costs and money for equipment.
Lund University was founded in 1666 and currently has 42,000 students. The Department for Experimental Medicine is a modern and vibrant place to work and study. The department counts 60 independent research groups and excellent core facilities. The Wallenberg Foundation has announced that they will fund 10 large starting grants in molecular medicine over the next few years to recruit new group leaders. One of these recruitments was Dr. Iben Lundgaard. The new research groups funded by the Wallenberg Foundation will stimulate the research environment and further expand the growing international environment at Lund University.
Principal investigator Iben Lundgaard has, during her Master degree in molecular biology, obtained experience from aging lab, Suresh Rattan, Na/K ATPase in Nobel laureate Jens Christian Skou's lab at University of Aarhus and apoptosis and calcium binding proteins in Martin Berchtold’s lab at University of Copenhagen. After a short internship in electrophysiology at University of Copenhagen, Iben started her PhD in the UK.
Iben Lundgaard did a PhD in neuroscience with Ragnhildur Thora Karadottir and Robin Franklin at University of Cambridge, UK, 2008-2012. The main findings of her PhD thesis were that growth factors neuregulin and BDNF interact with neuronal activity to control myelination and that remyelination after injury is dependent on NMDA receptors.
Dr. Lundgaard worked with Maiken Nedergaard at University of Rochester where the glymphatic system was discovered. During her time in the Nedergaard lab Dr. Lundgaard gained detailed knowledge on the glymphatic system, see for example the study on delivery of glucose from the CSF to the brain parenchyma via the glymphatic system. After 2 years, Dr. Lundgaard was promoted to assistant professor and stayed for another two and a half years to continue glymphatic research in multiple disease models. A number of projects from the Rochester lab are still on-going and will be continued in the new lab at Lund University.
The Lundgaard Lab is looking for PhD students and master students to work on glia biology, the glymphatic system and neurodegeneration and a postdoc to work on neuroimmunology.
For more details, please contact firstname.lastname@example.org.
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