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The Neuroscience Therapeutic Area at Janssen Pharmaceutica - Beerse is focused on research and development of neurodegenerative disease modifying therapeutics aimed at entering the clinical pipeline. While Alzheimer¿s and Parkinson¿s disease (AD/PD) research strategies have focussed on amyloid, Tau, synuclein pathologies and inflammation, complementary strategies targeting synaptic integrity and health are currently gaining momentum as critical, functional endpoint to consider in disease modification therapy. An Excitatory/Inhibitory imbalance, leading to hyperexcitability, seizures, neuronal loss was initially thought to occur at later stages of the diseases, however, synaptic dysfunction and subtle aberrant network activity are commonly found in patients already at earlier stages of diseases and therefore relevant for the development of (cognitive) symptoms. Moreover, understanding neuronal resilience and deficiency in mechanisms of neuroplasticity can aid at developing complementary class of drug targets that would normalize, at an early stage neural circuit dynamics ad cognitive capacity. In the In Vivo Systems Neuroscience group, we currently have an internship position for a master student, who will focus on development and implementation of a novel method to monitor synaptic activity following modulation of excitatory-inhibitory signaling in rodent models for neurodegenerative diseases.
description de la fonction
Job description: Implementation of multi-array silicon probes for in vivo multisite neural recordings following NR2a/NR2b modulation of NMDA receptors in anesthetized and freely moving animal models of neurodegenerative diseases.
Project description: Neurodegenerative disorders such as Alzheimer and Parkinson diseases (AD/PD) are characterized by gradual and irrevocable damage of neural networks, leading to progressive declines of neuronal plasticity and consequently to dramatic cognitive deficits. The investigation of plasticity in animal models of both diseases holds important implications for drug development and testing. Neural plasticity can be measured at multiple scales, from changes in individual neuron to a large-scale neural network in response to a stimuli.
Aim: Using an array of single or multi-shank silicon probes will enable us to repeated make multisite neural recordings at high spatiotemporal precision following pharmacological modulation of NMDA and AMPA components (local or multisite) in controls and neurodegenerative rodent models, while minimizing local ischemia/neuronal damage, thus providing a high resolution `window¿ on electrical activity in AD/PD modeled brains. In addition, electrical stimulation will inevitably activate many more unmonitored neurons than can be monitored (caused by synchronous activation of nearby neurons), making the separation between direct and population-mediated effects challenging. By sampling signals densely at multiple brain structures simultaneously such as to record from layers of neocortex and hippocampus, fast neuronal circuit activity (as involved in epilepsy/hyperexcitability) can be studied and the effect of NMDA/NR2a-2b drugs on firing rate spikes can be determined.
Responsibilities and duties: - Organisational Skills: The candidate can plan experimental tasks reasonably independently and to plan own experimental work according to agreed timelines. - Verbal Communication: The candidate is confident, accurate and open in 1-1 conversations, while being keen to train presentation skills in for example team meetings. - Interpersonal Skills: The candidate likes working alongside/together with peers and listens to the views of others. A preference for being a team player is considered a plus. - Applying technical/specialist knowledge: The candidate wants to learn to perform technical tasks according to high-quality criteria after adequate training and likes to develop the ability to work with limited support eventually. - Problem Solving: The candidate grasps essentials of a problem quickly and wants to develop over the trainee period to proactively offer realistic solutions as a full team member. - Inventiveness and initiative: The candidate shows initiative and volunteers new ideas and is able to provide and receive constructive criticism. - Interest: The candidate has an interest in mastering state-of-the-art neurobiological / neurophysiological techniques as well as some computing/analytic capabilities.
Qualifications: - Candidates applying for this in vivo project should possess certification for `carrying out procedures on animals¿ according to EU Directive 2010/63, Art 23 (FELASA-B or equivalent certificate e.g. UK: modules PIL: A +B (+C for proposals including animal surgery)) at the start of the internship.
Practical details: - Location: Beerse, Belgium - Duration: 10 -11 months - Timeframe: start Sep 2020 till July 2021 (can be discussed) - Others: This experimental work is also intended to lead to a scientific publication, hence an interest to invest in scientific writing is considered a plus point.
Requirement : The candidate must be a registered student for the entire course of the internship. Unfortunately, graduates that are currently not enrolled in a study program are not eligible for this internship. First choice is for trainees in Master in Drug Development (KU Leuven)
If you are interested in applying for this challenging internship, please send an e-mail to RA-RNDBE-InternBelg@ITS.JNJ.com, including your resume and a short motivation.