PhD Student (Animal Science and Fisheries)

Call for a Doctoral Scholarship

funded by the National Science Center as part of the project „Analysis of the molecular mechanism of phosphorylated α-synuclein and ubiquitinated protein accumulation caused by dopaminergic neuron-specific NFE2L1 gene knockout” no 2020/39/O/NZ5/02467

Discipline: animal science and fisheries

Research topic:

Parkinson’s disease is the second most common neurodegenerative disorder, affecting roughly 6,1 million people worldwide and one of the leading causes of disability. Symptoms include slowness of movement, tremor, and rigidity as well as depression and cognitive decline. While treatment options exist, they lose effectiveness over time and produce a plethora of side effects

NFE2L1 gene encodes a factor responsible for a variety of cellular functions among others the clearance of badly formed and unnecessary proteins. However, we lack direct evidence of the NFE2L1 gene’s involvement in the development of Parkinson’s disease.

In this project, we wish to explore this possible involvement and investigate the responsible mechanism. We will deactivate the gene specifically in the dopamine secreting neurons and we will observe the effects on mice behavior. The appearance of Parkinson-related symptoms will confirm that NFE2L1’s dysfunction could be the cause of Parkinson’s disease.

We will also perform these types of analyses on an in vitro model of neuronal development. Cells will be specially treated to cause their differentiation into neurons. The cells in which we have deactivated NFE2L1 will be compared to intact cells in the number of produced neurons, their growth, and other parameters.

Description of tasks:

Task 1: Generating an NFE2L1 dopaminergic neuron-specific knock-out mice

Task 2: General observation of mice behaviour and health indicators. Testing for Parkinson’s disease-like phenotype – motor symptoms, Testing for Parkinson’s disease-like phenotype – nonmotor symptoms

Task 3: Histopathological examination and immunostainig (ubiqutinated protein and alpha synuclein)

Task 4: Performing dopaminergic neuron Cell Isolation and RNAseq

Task 5: Knock-out/down of NFE2L1 with CRISPR/Cas9/siRNA in P19 cells and neuronal differentiation assay as well as transcription network analysis

Responsibilities in the project:

Selected person will work on the above mentioned tasks under supervision of the PI and post-docs. The project contains international cooperative aspect. Once the tasks are finished he or she will prepare draft for publications. Additionally, before publishing the tasks, the selected Ph. D. student will participate in international conference(s).