Job ID: 120181

PhD position in the Neurobiology of Ageing

Position: Ph.D. Student

Deadline: 20 September 2024

Employment Start Date: 1 November 2024

City: Mainz

Country: Germany

Institution: Mainz University Medical Center

Department: Institute of Anatomy

Description:

We are seeking a highly motivated PhD student to join us at the Johannes Gutenberg University Mainz, Germany, to study the role of the RNA binding protein TDP-43 in the neurobiology and neuropathology of ageing.

Nuclear loss or cytosolic aggregates of TDP-43 are a central hallmark of neurological diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It has been proposed that TDP-43 dysfunction or aggregation may be an important determinant of healthy vs. pathological ageing, and that by influencing the degree of this TDP-43 dysfunction / aggregation, it may be possible to shift neuronal pathologies toward a healthier trajectory. A detailed understanding of the molecular mechanisms and cellular consequences of TDP-43 dysfunction and aggregation is therefore critical for identifying potential diagnostic and therapeutic strategies.

A key determinant and indicator of brain health is the ability to maintain normal excitability of neuronal networks. Indeed, cortical hyperexcitability is an early feature of several neurodegenerative disorders, including ALS and FTD, and it can precede and predict disease progression. Early evidence in mouse models showed that TDP-43 overexpression can induce hyperexcitability and subsequent functional decline, indicating that altering network excitability may be one of the pathological mechanisms of TDP-43 aggregation. To date, however, little is known about this process, and several critical questions remain unanswered.

In the current consortium, we aim to address these questions in a multidisciplinary team that bridges two fields, i.e. the molecular and cellular biology of TDP-43 function and the study of neuronal networks and their functional output. We combine the expertise of three PIs  –  Dilja Krueger-Burg, Dorothee Dormann, and Michael Schmeisser – to span from in vitro assays to behavioral analysis in mouse models. In this manner, we will link molecular, cellular, network and behavioral dysfunction, as well as directly testing strategies to counteract TDP-43-mediated dysfunctions that are detrimental to healthy ageing.

In this context, we are offering a PhD position starting in November 2024. The successful candidate will be affiliated with the Focus Program Translational Neurosciences (FTN) of the Johannes Gutenberg University Mainz (https://www.blogs.uni-mainz.de/ftn-eng/), a member of the Rhein-Main Neuroscience Network (http://www.rmn2.de/). The doctoral degree will be granted through the Mainz Research School of Translational Biomedicine (https://www.unimedizin-mainz.de/transmed/phd-mdphd-in-translational-biomedicine.html).

Applications including a letter of motivation, CV, university transcripts, and contact information for two letters of recommendation, should be sent to Prof. Dilja Krueger-Burg (dkruegerburg@uni-mainz.de) by September 20, 2024.