PHD STUDENT POSITION “THE ROLE OF THE OREXIN NEUROPEPTIDE SYSTEM IN THE DISEASE MANIFESTATION OF MULTIPLE SCLEROSIS: EXPLORING THE THERAPEUTIC POTENTIAL OF PHARMACOLOGICAL INTERVENTIONS IN ANIMAL MODELS“ – 3 YEARS

Position.
Ph.
.
Student Deadline.
29 July Employment Start Date.
1 November Contract Length.
3 years City.
Camerino (Italy) and Basel (Switzerland) Country.
Italy Institution.
University of Camerino and Idorsia Pharmaceuticals Ltd (Basel, Switzerland) Department.
Description.
The Laboratory of Brain and Sleep Research is offering 1 PhD position in “theoretical and applied neuroscience” for a project entitled “.
The role of the orexin neuropeptide system in the disease manifestation of multiple sclerosis.
exploring the therapeutic potential of pharmacological interventions in animal models ”.
To apply.
https://www.
nicam.
t/bandi//bando-n-del- Project description Multiple sclerosis (MS) affects nearly 2.
million people globally, causing nerve damage in the brain and spinal cord and impairing the protective myelin sheath.
This leads to disabilities such as fatigue, depression, and cognitive issues, significantly impacting employment and quality of life.
A significant contributor to these symptoms is the lack of restorative sleep.
Chronic sleep insufficiency, affecting up to 50% of people with MS, is linked to impaired myelination, increased brain inflammation, and altered immune response.
MS can damage brain regions involved in regulating sleep and wakefulness, such as the orexinergic neurons in the hypothalamus, contributing to sleep disturbances.
Preclinical research using the experimental autoimmune encephalomyelitis (EAE) model suggests that orexins can mitigate inflammation and slow disease progression.
Additionally, modafinil, a stimulant, is often used off-label to help MS patients manage fatigue.
Therefore, the orexin system could represent a crucial pharmacological target to alleviate night-related sleep disturbances and counteract day-related fatigue and inflammation.
This project aims to explore the dual modulation of the orexin system in preclinical MS models.
the cuprizone mouse model and EAE.
By administering dual orexin receptor antagonists (DORAs) during sleep, we will investigate their effects on sleep improvement, remyelination, and well-being.
During waking, orexin agonists will be tested for their potential to reduce inflammation, disease progression, and fatigue symptoms.
Our approach involves behavioral, electrophysiological, morphological, and molecular analyses to understand the mechanisms by which improved sleep can promote remyelination and modulate immune responses.
Additionally, we will assess how stimulating the orexin system during wake can impact inflammation, disease progression, and fatigue.
This research could lead to novel therapeutic strategies for MS by targeting sleep disturbances and utilizing orexin-based treatments.
The scientific environment This research project will be carried out in collaboration with Idorsia Pharmaceuticals Ltd (Basel, Switzerland) where the PhD student will have the opportunity to spend 12 months to carry out part of the project.
The remaining time will be spent at the Brain and Sleep Research Laboratory of the University of Camerino (Italy).
The sleep team, led by Luisa de Vivo and Michele Bellesi, aims at understanding the functions and mechanisms of sleep in health and disease.
Our research combines morphological and functional methods of analysis in both animals and humans to investigate why sleep is beneficial for the brain at the molecular, circuit and behavioral level.
On one hand, we are focused on mapping the consequences of sleep impairment across the lifecycle and to characterize the interaction between sleep disruption and other environmental and genetic factors.
On the other hand, we are interested in the therapeutic potential of sleep enhancement to improve health and cognition at different levels.
To this aim, we are studying pharmacological and non-pharmacological approaches to mitigate neuropsychiatric and neurodegenerative conditions by targeting sleep.
The lab explores also scientific questions linking sleep to glial cells, gut microbiome, cellular metabolism, adipose tissue, torpor, etc., thanks to the collaboration with other research groups within the University of Camerino and outside.
Relevant publications and key interests of the research group can be found at https://www.
srlaboratory.
rg/.
The team consists of several post-doctoral fellows and PhD students with different backgrounds including biology, pharmacology, informatics, and physics.
Researchers have access to m 2 of animal facility equipped with systems for EEG/EMG and LFP recordings, in vivo calcium imaging in freely behaving rodents, automatic motion detection, apparata for behavioral tests, and a new human sleep laboratory.
Fully equipped labs for immunohistochemistry, light, confocal, and electron microscopy, cell culture, and molecular biology are available.
Preferred Research Skills and Competences The ideal candidate has a genuine passion for neuroscience and sleep research, a proactive attitude in studying relevant literature, formulate plausible hypothesis and experiments to test them.
Self-motivation, curiosity, and ability to work both alone and in team are essential characteristics.
Background in neurophysiology, interest in learning microscopy techniques, basic knowledge of Python or Matlab, and a propensity to care for details are desirable.
The doctoral candidate will receive training in histology, in vivo and ex vivo imaging (light and electron microscopy), electrophysiology in vivo, behavioural testing, molecular biology, and data analysis.
Pharmacological, chemogenetic and optogenetic approaches will be also experienced.
The University of Camerino (UNICAM) UNICAM is a ‘city campus university’ chartered in , with about undergraduate students, and 180 PhD candidates, of which ~40% are foreigners.
For a substantial number of programs in foreign languages and a high percentage of international students, UNICAM has been top rated for international orientation ( U-Multirank report).
Moreover, UNICAM hosts the International School of Advanced Studies, responsible for coordinating interdisciplinary PhD programs that span upon the major key research areas of the University, including Life and Health Sciences, and Science and Technology.
UNICAM has excellent research facilities including m 2 vivarium fully equipped for mouse and rat breeding, maintenance and behavioural testing, sleep monitoring and electrophysiology recordings, equipped histology labs, wet labs with all basic molecular biology and biochemistry equipment, light, confocal and electron microscopes.
UNICAM campus offers an interdisciplinary environment with experts in diverse fields of science, national and international collaborations with other universities and industry.
The campus offers also housing for students and excellent facilities for indoor and outdoor sports.