Job ID: 121662
Ph.D. position in the Laboratory of Cholinergic Signaling
Position: Ph.D. Student
Deadline: 30 April 2025
City: Prague
Country: Czech Republic
Institution: Institute of Physiology, Czech Academy of Sciences
Department: Laboratory of Cholinergic Signaling
Description:
The Institute of Physiology CAS is located in Prague, Czech Republic, and it is one of the leading research institutes in biomedicine in the Czech Republic. The Laboratory of Cholinergic Signaling investigates the expression and function of acetylcholine receptors in defined neuronal populations, primarily in the striatum and prefrontal cortex. We are using genetic mouse models, viral vectors, imaging techniques and behavioral analysis to determine how acetylcholine receptors shape neural circuits and the whole organism. We are also developing new approaches that would allow us to target the receptors selectively in defined neuronal populations by a combination of pharmacological and genetic techniques.
Project description:
Nicotinic acetylcholine receptors expressed by specific neuronal types in the control of ASD-like symptoms
Nicotinic acetylcholine receptors (nAChRs) have been implicated in autism spectrum disorders (ASD), but similar to other disorders, it is challenging to use them as an effective therapeutic target. One of the reasons is their widespread distribution in the brain and, thus, the difficulty in controlling them selectively in circuits and neurons where needed. In the newly started project, we aim to determine how nAChRs expressed in specific neuronal types in the prefrontal cortex contribute to the control of ASD-like behavioral symptoms in mice. To do that, we will use ASD mouse models to investigate the expression of nAChRs in specific neuronal types; then, we will modulate the nAChRs’ activity in a neuronal-type-specific manner and examine the effects on neural circuits and ASD-like behavior. In addition, we will use a pair of an engineered bacterial enzyme nitroreductase and a nicotinic ligand masked with a nitroaryl group to selectively target the intracellular pool of nAChRs in specific neuronal populations. We will aim to selectively modulate the expression of nAChRs in specific neurons and determine the functional and behavioral effect of these changes.
The successful candidates for the Ph.D. positions are supposed to participate primarily in some of the following areas of the project:
- Determining the expression of individual subtypes of nAChRs in selected neuronal populations in the mouse prefrontal cortex by RNAscope and FISH
- Inhibition/activation of the nAChRs expression in specific neuronal types in vivo by the combination of neuronal-type-specific viral vectors and shRNA or CRISPRa approaches
- Determining the effect of the selective nicotinic modulation on behavior and cognition by behavioral testing of ASD mouse models in touchscreen-equipped operant boxes
- Determining the effect of selective nicotinic modulation on neuronal activity and plasticity by Ca2+ imaging and gene expression analysis.
- Validating the “enzyme-masked ligand” pair in vitro and in vivo, testing the distribution and degradation of the ligand and determining its activity.
We are looking for highly motivated candidates with a suitable background and interests to take part in the above-described activities. To apply, please send your CV and a motivation letter to the email address below.