Cellular Neurology - PhD

The Department of Cellular Neurology at the Hertie Institute for Clinical Brain Research and the German Centre for Neurodegenerative Disease in Tübingen, Germany, is seeking several

PhD students

for the following projects:

1. Transmission and spreading of cerebral amyloidosis. We are looking for a PhD student with an interest in the mechanisms of cerebral amyloidosis, the hallmark pathology of Alzheimer’s disease. We have shown that injection of Aβ-containing brain extract into young amyloid precursor protein (APP) transgenic mice induces cerebral β-amyloidosis by a mechanism reminiscent of prion disease (see Meyer-Lühmann et al., Science 313: 1781, 2006; Eisele et al, Proc Natl Acad Sci USA, 106:12926, 2009). Towards the identification of this amyloid-inducing activity and mechanisms of amyloid induction and spreading, we are looking for a PhD student with an interest in structural and biochemical aspects of Aβ and preferentially with experience in transgenic mouse work. The student will work closely together with other lab members in their endeavor to understand the molecular pathogenesis of cerebral amyloidosis and related neurodegeneration.

Contact: Mathias Jucker (mathias.jucker(at)uni-tuebingen.de)

2. The cellular propagation of protein aggregates. Propagation of proteopathic protein aggregates from cell to cell are an emerging mechanism how proteopathic lesions spread and may induce degeneration along neural pathways. The relevance of such in-vitro findings is underlined by in-vivo observations of induction and  spreading of Abeta and tau lesions in the brain (Science 313: 1781, 2006; Nat Cell Biol 11: 909, 2009). Molecular mechanisms remain, however, widely obscure but might be conserved (Science 326: 1337, 2009). We are looking for a PhD student with an interest in studying the cellular uptake, propagation, and spreading of protein aggregates in cell culture and in vitro models. The student will work closely together with other lab members in their endeavor to understand the molecular pathogenesis of cerebral amyloidosis and related neurodegeneration.

Contact: Frank Baumann (f.baumann(at)medizin.uni-tuebingen.de)

3. Multiphoton microscopy to image Alzheimer lesions in transgenic mice. Amyloid plaques and neurofibrillary tangles are the hallmark lesions of Alzheimer´s disease. Aβ is the main constituent of amyloid plaques whereas tau is the main constituent of neurofibrillary tangles. Numerous in-vitro assays have been performed with Aβ and tau to investigate kinetics and mechanisms of fibril formation. However, only recently the imaging of amyloid formation with non-invasive techniques under live conditions has been achieved in transgenic mice (Meyer-Luhmann et al., Nature 451: 720, 2009; Bolmont et al., J. Neuroscience 28: 4283; 2008). We are looking for a highly motivated PhD student who will use novel dyes and recently developed 2-photon-imaging techniques to advance the imaging of the amyloid and tau lesions towards a better understanding of the pathogenesis and the development of biomarkers of the disease. For this project previous experience in stereotaxic surgery in mice is an advantage.

Contact: Bettina Wegenast-Braun und Mathias Jucker (bettina.braun(at)uni-tuebingen.de or mathias.jucker(at)uni-tuebingen.de)

4.  The role of microglia and infiltrating bone marrow-derived monocytic cells in central nervous system pathology. Microglia, the resident immune effector cells of the brain, constantly monitor their microenvironment for pathogens.  When foreign entities are encountered, microglia undergo phenotypic alternations enabling them to clear debris, promote tissue repair and recruit other immune cells.  However, in cases of chronic inflammation, as occurs in Alzheimer’s disease (AD), microglial activation may be harmful and exacerbate disease progression (Varvel et al., Journal of Clinical Investigation 119:3692, 2009). However, the pathogenesis is likely to be more complex and other cell types, such as bone marrow-derived monocytic cells, might infiltrate CNS tissue and augment amyloid pathology. Building on a mouse model in which we can deplete >90% of microglia (Grathwohl et al., Nature Neuroscience 12:1361, 2009), we have developed a new mousel model which allows the repopulation of the microglia-depleted mouse brain with bone marrow-derived monocytic cells.  We are now seeking a PhD student with an interest in inflammatory processes in the CNS and in AD to use these mouse models to study the neuroinflammation in AD. The student should preferably have experience with transgenic mice and histological techniques. Further, experience with sterotaxic surgery would be ideal. The student will work closely with other members of the neuroinflammatory group to understand the role of microglia in disease and in maintaining brain health.

Contact: Nicholas Varvel (nicholas.varvel(at)uni-tuebingen.de)