Neurosciences
Exploring the Therapeutic Potential of Young Donor FMT in Modulating Gut Dysbiosis, Glial Senescence, and Parkinson's Disease Pathology.
Annotation and Objectives:
Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of alpha-synuclein (aSyn) in Lewy bodies. Emerging evidence highlights the gut microbiome’s role in neurodevelopment and brain health through neurotransmitter modulation. PD patients exhibit altered gut microbiota, with reduced diversity and increased pathogenic bacteria, contributing to gut inflammation, neuroinflammation, and disruptions in the gut-brain axis. Aging is a major PD risk factor, leading to the accumulation of senescent microglia and astrocytes, particularly in the substantia nigra (SN). This shift from neuroprotective to pro-inflammatory glial states exacerbates neurodegeneration. However, the exact contribution of senescent glial cells to PD remains unclear. Interestingly, faecal microbiota transfer (FMT) from young to aged mice has been shown to reverse hallmarks of aging, suggesting a potential therapeutic avenue. This project aims to: 1. Identify PD-associated pathogenic gut bacteria using 16S rRNA sequencing and targeted qPCR, and assess their integration in mice via oral or rectal administration. 2. Investigate how these bacteria induce neuroinflammation, glial senescence, and dopaminergic neurodegeneration in the SN. 3. Evaluate the therapeutic potential of transferring healthy young human faecal microbiota into PD mouse models to reduce neuroinflammation, glial senescence, and dopaminergic neuron loss. This study will provide new insights into the gut microbiome’s role in PD and explore microbiome-based interventions as potential disease-modifying strategies.
Funding of the research
Currently the project is funded for around 4 years from AZV - NW26-04-00432. The PhD student is encouraged to apply for some external funding like Brno PhD talent as well. Also, it is possible once the pilot data will be generated, more funding can be applied at both National and European Union level.
FTE possibility: 0.3 to 0.5
Eligibility criteria on the student:
➢ M.Sc., M.Pharm in neuroscience, pharmacology, natural science, quantitative science, or a related discipline
➢ Solid experience in handling the rodents and behavioural studies for motor and memory impairment. Knowledge of stereotaxic surgery is must.
➢ Experince in molecular biology techniques like RT-PCR, Western blot and immunohistochemistry
➢ Strong analytical skills, intrinsic motivation, and organization skills
➢ Advanced English communication skills
Requirements for the student according to the Board for the PhD studies Neuroscience at MU Minimum publishing activity of the student within the Ph.D. study presents one review article in peer-reviewed journal and one original article in a journal with IF over the median of the
field, both related to the topic of the dissertation. completion of an international study period of at least one month in duration, which is mandatory for full-time doctoral students, or collaboration on an international project including participation in regular project team meetings with results published or presented abroad, or other forms of direct participation in international collaboration. participation in teaching of Bachelor’s and Master’s programmes or other educational activities in the workplace; you may also be entrusted with supervising or reviewing the final theses of students of Bachelor’s or Master’s programmes, helping with examination organisation, etc. Completion of compulsory courses: courses designed to broaden and enhance your knowledge in the field beyond the scope of Master’s studies, courses designed to refine specialised knowledge, specialised seminars and lectures.
Supervisor:
Amit Khairnar, Junior Research Group Leader, ICRC FNUSA, Ph.D.
There are 4 PhD students who already defended their PhD under the supervision of Amit Khairnar. The PI has published more than 43 publications in international and peer reviewed impacted journals having H index of 17 and total number of citations more than 1000. The PI was successful in receiving the Marie Curie fellowship. He was also the awardee of prestigious Ramalingaswami fellowship for 5 years. He has completed so many projects and has rich experience in development of progressive mouse models of PD and understanding the pathology behind development of alpha synuclein pathology. In case of questions, it is possible to contact the supervisor: amit.khairnar@fnusa.cz
Mentor: Jana Rudá, PharmD, PhD (Associate Professor)
Use of point-of-care ultrasound and interventional neurosonology methods in neurology
Annotation and Objectives:
The aim of the PhD project is to develop, implement and evaluate point-of-care ultrasound and interventional neurosonology methods in neurology and neurointensive care. Point-of-care ultrasound and ultrasound guided interventional methods will be developed in multiple modules. There will be two main areas of implementation and evaluation of the modules:
1. Development and implementation of the point-of-care ultrasound methods
2. Proof-of-concept studies for each module
3. Development, implementation and evaluation of the World Organization of Neurosonology Educational programme
Number of applicants: 1
Connection to grant project:
FTE possibility: Expenses will be covered by the North West Anglia NHS Foundation Trust if appropriate.
Eligibility criteria on the student:
- Master's or equivalent degree in science related to the topic.
- Passing the introductory interview in English about the dissertation topic
- English language at least at B2 level according to the Common European Framework of Reference
- willingness to participate in international cooperation
As part of the PhD studies:
- fulfilling the requirements of an individual study plan
- completion of courses required in the Neuroscience program, specialization Neuroscience
- Publication activity - at least 3 impacted publications, of which 2 original and at least 2 first authorships
- completion of a foreign internship of at least 1 month
-cooperation on international projects
Supervisor:
Radim Licenik, Ph.D., M.D., M.Sc., FESO, FRCP (London)
Publication activity: I am author or co-author of more than 30 articles, two book chapters and five monographs and textbooks in the field of stroke medicine, neurology and guidelines. Current projects: My current research activity centres around use of ultrasound methods in acute, emergency, and stroke medicine and neurology. I have been developing relevant point of care ultrasound algorithms such as focused cardiac ultrasound (FoCUS) as well as multiple point-of-care ultrasound (POCUS) modules used in both pre-hospital and hospital emergency care, acute medicine, emergency and general neurology. My other research activities are also focused on developing electrophysiology methods in emergency neurological care, young stroke patients and pre-hospital neurological emergency care with special projects in use of mobile stroke units. I am actively involved in work of different committees of the World Organisation of Neurosonology, European Stroke Organisation and Pre-hospital Stroke Treatment Organisation.
Mentor:
Dr Osian Llwyd, Wolfson Centre for Prevention of Stroke and Dementia, University of Oxford, UK