Head of PhD Programme: Joanna Sypecka MD PhD MMRI Prof.
Department of Restorative Neurobiology
phone (+48) 22 60 86 508, This email address is being protected from spambots. You need JavaScript enabled to view it.
Room B123
PhD Student Affairs Office: Aleksandra Bilmin MA Eng.
Administration Office
phone (+48) 22 60 86 453, This email address is being protected from spambots. You need JavaScript enabled to view it.
Room B114
HELPFUL INFORMATION & DOCUMENTS
Doctoral Schools:
- DOCTORAL SCHOOL OF INFORMATION AND BIOMEDICAL TECHNOLOGIES POLSH ACADEMY OF SCIENCES
- DOCTORAL SCHOOL OF TRANSLATIONAL MEDICINE
RECRUITMENT - Projects within Doctoral School of Translational Medicine
Project number: OPUS nr. 2019/33/B/NZ3/02889
1. Supervisor:
Full name and academic title. dr hab. n. med. Magdalena Czeredys
2. Supervisor’s email: This email address is being protected from spambots. You need JavaScript enabled to view it.
3. Auxiliary supervisor, if applicable: not applicable
Full name and academic title.
4. Research unit:
Name of the department or institute.
Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute Polish Academy of Sciences
5. Project title – English:
Understanding the causes of synaptic dysfunction in the pathology of juvenile and adult forms of Huntington’s disease using 2D striatal neuronal cultures differentiated from hiPSCs.
6. Project title – Polish:
Zrozumienie przyczyn zaburzeń synaptycznych w patologii młodzieńczej i dorosłej formy choroby Huntingtona z wykorzystaniem hodowli 2D neuronów striatalnych różnicowanych z hiPSC.
7. Scientific discipline:
Medical sciences
8. Project description:
Huntington’s disease (HD) is an incurable neurodegenerative disorder. It is characterized by an abnormal number of CAG repeats encoding glutamine in the HTT gene, leading to the aggregation of mutant huntingtin protein, which is toxic to neurons in the striatum, causing synaptic dysfunction. Depending on the length of the CAG repeats in HTT gene, Huntington’s disease can manifest as either adult-onset or juvenile-onset. The aim of the project is to understand the molecular causes of synaptopathy in juvenile and adult forms of Huntington’s disease using striatal neurons obtained in vitro by differentiation of human induced pluripotent stem cells (hiPSCs) from HD patients and healthy individuals, as well as to identify new therapeutic targets. To elucidate the pathology of HD, genetic engineering methods, electrophysiological, as well as biochemical and molecular biology techniques will be employed.
10. Relevant literature:
Latoszek E, Czeredys M. Molecular Components of Store-Operated Calcium Channels in the Regulation of Neural Stem Cell Physiology, Neurogenesis, and the Pathology of Huntington's Disease. Front Cell Dev Biol. 2021; 9:657337, https://doi.org/10.3389/fcell.2021.657337
11. Candidate requirements:
- Master’s degree in biology, biochemistry, or a related field
- Experience in laboratory work and familiarity with basic techniques in biochemistry, molecular biology, cell biology, and/or microscopy imaging
- Experience in cell culture maintenance
- Previous experience with hiPSC culture and their differentiation into neurons or organoids; genome editing; and electrophysiology will be considered a significant advantage
- Motivation, passion, and an enthusiastic approach to experimental work
- Ability to work independently as well as part of a team
- Strong organizational and analytical skills
- Proficiency in spoken and written English, with the ability to use English in scientific work
- Interest in neurodegenerative and neurodevelopmental diseases
- Willingness to learn and take on new challenges
- Active participation in scientific conferences
12. Scholarship amount:
Before the mid-term evaluation, the monthly scholarship will amount to: PLN 3,685 gross (PLN 3,270 net).
After the mid-term evaluation, the monthly scholarship will amount to: PLN 5,350 gross (PLN 4,747 net).
An additional scholarship from the doctoral school is awarded annually (PLN 1,200 net/per month).
13. Number of positions available: Planned number of PhD positions. one position
Project number: SONATA BIS 13, 2023/50/E/NZ4/00550 oraz OPUS 20 LAP, 2020/39/I/NZ4/01031
1. Supervisor:
Prof. dr hab. n. med. Agata Adamczyk
2. Supervisor’s email: This email address is being protected from spambots. You need JavaScript enabled to view it.
3. Auxiliary supervisor:
Dr Anna Wilkaniec
4. Research unit:
Zakład Komórkowej Transdukcji Sygnału
5. Project title – English:
The role of parkin in metabolic and immunological disorders in an alpha-synuclein-induced mouse model of Parkinson's disease.
7. Scientific discipline
medical sciences
8. Project description in polish and english:
Parkinson’s disease (PD) is a common neurodegenerative disorder associated with the progressive loss of dopaminergic neurons and the accumulation of α-synuclein (α-syn) aggregates in the brain. Previous in vitro studies conducted in the Department of Cellular Signaling have shown that α-syn impairs mitochondrial function and reduces the level of parkin — a protein essential for proper mitochondrial activity. Damaged mitochondria can, in turn, initiate pro-inflammatory responses and oxidative stress, contributing to neurodegeneration.
The aim of the project is to verify the hypothesis that α-syn-induced loss of parkin function plays a keyrole in mitochondrial dysfunction, and that damaged mitochondria trigger abnormal glial activation, leading to neurodegeneration.
Experimental model: The study will be conducted on a mouse model of PD induced by intrastriatal injection of α-syn oligomers. The following experimental groups will be used:
- 3-month-old male C57BL/6J wild-type mice,
- parkin knockout mice (strain B6.129S4-Prkntm1Shn/J),
- mice with parkin overexpression (strain B6;FVB-Tg(Prnp-PARK2)196Kfw/EkraJ).
Analyses will be performed at 30, 90, and 180 days after α-syn administration.
Research tasks:
1. Evaluation of structural and metabolic changes in the mouse brain.
2. Analysis of molecular and biochemical parameters of mitochondrial damage.
3. Assessment of oxidative stress levels and markers of inflammatory processes.
4. Analysis of microglial and astrocyte numbers and activation states.
5. Performance of behavioral tests characteristic of PD in the same experimental model.
The proposed study will provide new insights into the role of parkin in the regulation of mitochondrial function and the development of inflammatory responses in the brain. The results may help identify new therapeutic targets for disease-modifying interventions in Parkinson’s disease.
10. Relevant literature:
Jęśko H, Lenkiewicz AM, Wilkaniec A, Adamczyk A. The interplay between parkin and alpha-synuclein; possible implications for the pathogenesis of Parkinson's disease. Acta Neurobiol Exp (Wars). 2019;79(3):276-289. PMID: 31587020.
Wilkaniec A, Lenkiewicz AM, Babiec L, Murawska E, Jęśko HM, Cieślik M, Culmsee C, Adamczyk A. Exogenous Alpha-Synuclein Evoked Parkin Downregulation Promotes Mitochondrial Dysfunction in Neuronal Cells. Implications for Parkinson's Disease Pathology. Front Aging Neurosci. 2021 Feb 24;13:591475. doi: 10.3389/fnagi.2021.591475. PMID: 33716707; PMCID: PMC7943853.
Wilkaniec A, Lenkiewicz AM, Czapski GA, Jęśko HM, Hilgier W, Brodzik R, Gąssowska-Dobrowolska M, Culmsee C, Adamczyk A. Extracellular Alpha-Synuclein Oligomers Induce Parkin S-Nitrosylation: Relevance to Sporadic Parkinson's Disease Etiopathology. Mol Neurobiol. 2019 Jan;56(1):125-140. doi: 10.1007/s12035-018-1082-0. Epub 2018 Apr 21. PMID: 29681024; PMCID: PMC6334739.
