Recruitment 20/21-1

  • May 25, 2020 -  recruitment opens

  • June 7, 2020 - deadline for applications

Research projects for admissions 2020/2021-1:


Linking abnormal Ca2+ signaling and the unfolded protein response with Huntington’s disease pathology in both YAC128 mouse model and iPSC-derived neurons from HD patients.

Prof. Jacek Kuźnicki, PhD; Magdalena Czeredys, PhD, Laboratory of Neurodegeneration

Description: Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by the aggregation of mutant huntingtin and degeneration of medium spiny neurons (MSNs) in the striatum. Abnormal Ca2+ signaling is considered as an early event in HD pathology since disturbances in Ca2+ homeostasis were found in HD models and postmortem samples from HD patients. One of the pathways for Ca2+ signaling is store-operated calcium entry (SOCE). The activation of inositol-(1,4,5)triphosphate receptor 1 (IP3R1) results in Ca2+ release, which decreases ER Ca2+ content and activates Ca2+ influx through SOC channels. Elevated SOCE and increased IP3R1 activity was previously reported in MSNs from the transgenic model of HD, YAC128. The project is based on the hypothesis that neurodegeneration in HD is induced by disturbances in Ca2+ signaling in neurons. Previously we found that huntingtin-associated protein 1 (HAP1) that is overexpressed in striatal neurons and binds to mutant huntingtin causes dysregulation of Ca2+ signaling by increased activation of both SOCE and IP3R1 receptors. We intend to examine the link between dysregulated Ca2+ signals and neuronal cell death in HD. The experiments will be performed in YAC128 MSNs cultures and neurons delivered by the reprogramming of fibroblasts from HD patients with the application on CRISPR/Cas9-based editing strategies and Ca2+ signaling inhibitors.

Aim: The project aims to investigate whether and how the disturbed Ca2+ homeostasis affects HD pathology. A Ph.D. project related to this issue will be done using different HD models. One position is available in the project. We are looking for a person interested in neurobiology, with experience in working with animal models (mice, zebrafish), cell cultures, and biochemical techniques (immunoprecipitation, western blot). Knowledge/experience in iPSCs cultures is welcome.

Number of positions available: 1

Source of funding: NCN/OPUS grant

Contact: This email address is being protected from spambots. You need JavaScript enabled to view it. 


Cytoplasmic polyadenylation as a central regulator of physiological processes

Prof. Andrzej Dziembowski, PhD, Laboratory of RNA Biology

Description: Poly(A) tails generated by canonical poly(A) polymerases during mRNA 3’ formation are essential for mRNA stability and translation. It is now appreciated that poly(A) tail dynamics is more complex than previously suspected; deadenylated mRNAs in the cytoplasm can be degraded, uridylated or stored in a dormant state to be later re adenylated to activate protein synthesis. Cytoplasmic polyadenylation was mostly studied in the context of gametogenesis and in synapses, where the transcriptional activity is limited. Surprisingly, mouse lines devoid of the well known cytoplasmic poly(A) polymerase GLD2 display no apparent phenotypes. We recently described a novel family of cytoplasmic poly(A) polymerases, TENT5 (FAM46), comprising four members in vertebrates (Mroczek et al. & Bilska et al. Nat Comm 2017,2020). TENT5C acts as a tumor suppressor in multiple myeloma, while mutations in TENT5A lead to a rare disease osteogenesis imperfecta. We have generated KO mouse models for all TENT5 genes and detected a variety of different phenotypes affecting several organs and biological processes: gametogenesis, growth, skeletal development, hematopoiesis, immune response, and behavior. Moreover, analysis of the KO of worm TENT5 orthologue revealed dysfunction of innate immunity. Thus, TENT5 proteins contribute significantly to metazoan physiology and, more generally, that cytoplasmic polyadenylation plays a much broader role than previously anticipated, opening a new area of important research.

Aim: The project aims is to dissect functions and mechanisms of cytoplasmic polyadenylation by TENT5 in innate immunity, erythropoiesis, and neuronal physiology. Unique animal models constructed using CRISPR/Cas9, combined with advanced transcriptomic and proteomic approaches, will be used to achieve our goals. Several positions are available in the lab. The exact PhD project will depend on the particular skills and preferences of the student. We are looking for students with experience in work with animal modes (mouse, C. elegans), RNA biology, or bioinformatics.

Number of positions available: 4

Source of funding: NCN/Norway grants/FNP/Horizon2020 era chairs

Contact: This email address is being protected from spambots. You need JavaScript enabled to view it. 


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