PhD Opportunity in Neurobiology

100%

Researchers at the Neurobiology Laboratory for Brain Aging and Mental Health, led by Prof. Anne Eckert, are fascinated by what impairs neuronal functions during aging and neurodegenerative disorders and how this impairment can be prevented with specific regard to the involvement of mitochondria.

The research group is currently looking for a talented and motivated PhD student to work on a new project focused on mitochondria and tau pathology.

Abnormal tau protein hyperphosphorylation and aggregation is an important characteristic of Alzheimer's disease (AD) and more than 20 other serious neurodegenerative diseases. Abnormal tau has been shown to impact every aspect of mitochondrial function, including bioenergetic activity, dynamics, quality control and transport.

Recent outstanding discoveries have highlighted mitochondrial transfer between brain cells, namely between neurons and astrocytes. This intercellular mitochondrial transfer (IMT) has been shown to exert beneficial effects, such as increasing bioenergetics in recipient cells.

However, whether astrocyte-neuron mitochondrial transfer is impaired in AD-related tauopathy, and the therapeutic efficacy of enhancing mitochondrial transfer remain unknown.

Therefore, the aim of the project is to investigate the mechanisms and therapeutic efficacy of IMT in tauopathy. This project will constitute an important basis for modeling the molecular and cellular factors contributing to tau-induced bioenergetic deficits and will test a therapeutic approach based on mitochondrial transplantation.

Your position

You will apply state-of-the-art multi-step processes including innovative tools such as advanced human cellular systems (induced pluripotent stem cells (iPSC)-derived astrocytes and neurons bearing tau mutations), tools in molecular biology to assess changes in metabolic/ oxidative stress state (e.g. mitochondrial bioenergetics/ respiration), as well as flow cytometry and fluorescence microscopy.

Expertises which will be acquired during the training:

• Induced-pluripotent stem cells (iPSC) culture and differentiation into astrocytes and neurons.
• Staining, flow cytometry and microscopy techniques
• Real-time monitoring of mitochondrial respiration
• Writing of scientific publication
• Poster / oral presentation

Your profile

The candidate should have an increased interest in neuroscience and basic knowledge of neurodegenerative pathologies. Completion of a master's degree in neuroscience or molecular biology combined with experience in cell culture techniques is an advantage.
The ability to work in a team and to communicate in English is essential.

We offer you

To work in an international team at the Transfaculty Research Platform, Molecular & Cognitive Neuroscience, University of Basel (https://mcn.unibas.ch/de/divisions/neurobiology/).
Research team composition: Researchers: 1 - PhDs: 2 - PostPhDs: 2 - Technicians: 1 - Others: 1
Salary: 3 years full time, PhD salary in accordance with SNSF doctoral salary guideline
The University of Basel is an equal opportunity employer. Candidates will receive scientific mentoring and academic training with the aim to develop an independent research profile.
Place of work: Neurobiology Laboratory for Brain Aging & Mental Health, Transfaculty Research Platform, Molecular & Cognitive Neuroscience, Psychiatric University Clinic, University of Basel, Basel (Switzerland).
Head: Prof. Dr. Anne Eckert, Junior advisor: Dr Amandine Grimm
Address: Wilhelm klein Str. 27, 4002 Basel, Switzerland
Email: anne.eckert@upk.ch; Phone number: +41 61 325 5487

Main publication(s)
1st: Demetrius LA, Eckert A, Grimm A (2021) Sex differences in Alzheimer's disease: metabolic reprogramming and therapeutic intervention. Trends in Endocrinology & Metabolism, 32:963-979. doi.10.1016/j.tem.2021.09.004
2nd: Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, Beal MF, Bergersen LH, Brinton RD, de la Monte S, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nature Reviews Drug Discovery 2020, 19, 609-633, doi:10.1038/s41573-020-0072-x
3rd: Schmitt K, Grimm A, Dallmann R, Oettinghaus B, Restelli LM, Melissa Witzig, Ishihara N, Mihara K, Ripperger JA, Albrecht U, Frank S, Brown SA, Eckert A (2018), Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metab. doi: 10.1016/j.cmet.2018.01.011.