Recruitment 20/21-3

  • December 8, 2020 - Recruitment announcement published

  • December 22, 2020 - Start of the recruitment

  • January 5, 2021 - Deadline for documents submission

 

Research projects for admissions 2020/2021-3:

1. Title: Rac1 contribution to brain connectivity impairments and neuropsychiatric disorders in Tuberous Sclerosis Complex (NCN/OPUS)

Supervisor: Prof. Jacek Jaworski

Auxiliary Supervisor: Justyna Zmorzyńska, PhD

Institute: International Institute of Molecular and Cell Biology in Warsaw

Laboratory: Laboratory of Molecular and Cellular Neurobiologylular Neurobiology

Project description:

During the brain development specific cellular events, including establishment of neural polarity, axon elongation, and synapse formation, happen in a temporally and spatially controlled manner to establish connectivity. These temporal and spatial boundaries are created by tight regulation of intrinsic and extrinsic factors. One of major components that may perform this regulation during connectivity development is Rac1 as it links plasma membrane receptors with actin dynamics. Also, mammalian target of rapamycin (mTOR) integrates intra- and extracellular factors. The diseases associated with over-expression of mTOR usually exhibit impairments of the brain development and neuropsychiatric phenotypes that do not necessarily correlate with mutation burden or cannot necessarily be explained by levels of mTOR activation. One of the examples is Tuberous Sclerosis Complex (TSC) in which neuropsychiatric disorders like autism spectrum disorder, intellectual disability, or anxiety do not fully correlate with mTOR expression levels, epilepsy, or tumor burden. Therefore, other molecular pathways must interact with mTOR pathway in order to produce these phenotypes. Our results and preliminary data suggest that Rac1 pathway and its diverse inputs may participate in the regulation of neuropsychiatric disorders in TSC through control of connectivity formation during development. The project will be conducted using zebrafish TSC model.

Aim:

The main objective of this project is to unravel how the interplay between various pathways that converge on Rac1 may participate in the brain connectivity and underlie TSC-associated neuropsychiatric disorders. The project will include behavioral testing, extensive microscopy imaging and image analysis, and transcriptome analysis.

Requirements: 

  1. Master’s degree in Biology, Biochemistry, Bioinformatics, or related area

  2. Solid understanding of the principles of molecular and cellular biology; knowledge on brain development, neuroscience, or computer vision will be a plus

  3. Willingness to work with zebrafish animal model

  4. Previous laboratory experience in basic molecular biology, biochemistry techniques, and/or imaging experience

  5. Prior experience in NGS, and/or working with animal models (mouse or zebrafish), as well as basic programming skills would be an advantage although not essential

  6. Ability to communicate fluently in English and a collaborative attitude

Number of positions available: 1

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

2. Title: Identification of novel vulnerabilities of VPS4B-deficient cancer cells (NCN/OPUS)

Supervisor: Prof. Marta Miączyńska

Auxilliary Supervisor: Ewelina Szymańska, PhD

Institute: International Institute of Molecular and Cell Biology in Warsaw

Laboratory: Laboratory of Cell Biology

Project description:

One of the key challenges in oncology is to effectively kill cancer cells while leaving healthy cells intact. To meet this goal, precision oncology aims to tailor anti-tumor therapies to individual genetic changes in cancer cells of a given patient. To provide new targets for precision oncology we need to understand the relationship between the genetic alterations of cancer cells and the dependencies (vulnerabilities) they cause. 

VPS4A and VPS4B enzymes together with the Endosomal Sorting Complex Required for Transport (ESCRT) machinery are involved in membrane remodeling during e.g. endocytosis, cell division, and plasma membrane repair. In our previous project, we identified VPS4B deficiency as a selective weakness of colorectal cancer cells with chromosome 18q deletion. We also demonstrated that survival of VPS4B-depleted cancer cells depends on the presence of VPS4A and characterized the molecular consequences of simultaneous depletion of VPS4 proteins that lead to cell death (more details in Szymańska et al, EMBO Mol Med, 2020). Very probably, VPS4B deficiency makes cancer cells more vulnerable not only to VPS4A loss but also to other perturbations affecting gene(s) cooperating with VPS4B in cellular processes essential for life.

Aim:

We aim to identify and characterize novel vulnerabilities of VPS4B-deficient cancer cells among candidates selected from datasets of the Cancer Dependency Map Project (Broad Institute). To this end, we will examine the impact of simultaneous depletion of VPS4B and a selected candidate on in vitro and in vivo growth of cancer cells. Further, we will elucidate the consequences of depletion of VPS4B and a candidate for cancer-relevant cellular processes, e.g. endocytosis, cytokinesis and migration.

Requirements:  

  1. Master's degree in biology, biochemistry or related field.

  2. Solid understanding of the principles of cell and molecular biology.

  3. Previous experience in laboratory work and familiarity with basic molecular biology techniques.

  4. Written and spoken fluency in English.

  5. Good interpersonal skills and a collaborative attitude.

Number of positions available: 1

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

3. RNA-Protein Interactions in Human Health and Disease (NCN/DIOSUCRI)

Supervisor: Gracjan Michlewski, PhD, DSc

Institute: International Institute of Molecular and Cell Biology in Warsaw

Laboratory: Laboratory of RNA-Protein Interactions

Project description:

RNA-binding proteins (RBPs) are key molecules that control gene expression through RNA-protein interactions. Consequently, they contribute to cellular homeostasis, normal development and majority of human diseases. Importantly, new RBPs are being discovered by high-throughput proteomics, but we still have a limited understanding of their function.

RNA viruses have caused several epidemics in the 21st century. Taking influenza A virus (IAV) infection as an exemplar, it kills 250,000 to 500,000 people annually and generates a significant global socioeconomic burden. Importantly the emergence of COVID-19 pandemic caused by an RNA virus SARS-CoV-2 continue to have catastrophic consequences on public health and world economy. Thus, a detailed molecular understanding of host-virus interactions is imperative in order to know how best to inactivate these viruses and prevent major disruptions in the future.

We have recently discovered and started characterising novel RNA binding protein – E3 ubiquitin ligase TRIM25 (Choudhury et al. 2014; Choudhury et al. 2017). TRIM25 belongs to a large family of tripartite motif-containing proteins (more than 80), most of which have E3 ubiquitin ligase activity. Many of TIRIMs are positive or negative regulators of innate immune response pathways. Importantly, TRIM25 is emerging as a key factor in the innate immune response to RNA viruses (including IAV, CoV, dengue virus and many others). Despite the essential involvement of TRIM25 in viral RNA-induced innate immunity, its RNA-binding functions are still poorly understood.

Aim:

With this project, we aim to take advantage of an assembled multi-disciplinary team to uncover the roles of the novel RNA-protein interactions in the antiviral response to selected RNA virus infections. We hypothesise that TRIM25 binds directly to viral RNAs to restrict virus propagation. We also hypothesise that other members from TRIM family bind RNA. Finally, we hypothesise that specific host RBPs bind to virus derived RNAs and inhibit or augment innate immune response. In summary, this project has the potential to make crucial contributions to understanding the innate immune response to RNA viruses and provide a platform for the development of novel, RNA-based antiviral therapeutics.

Requirements:

  1. MSc degree in biology, biochemistry or related field

  2. Solid knowledge of the principles of cell and molecular biology, virology or biochemistry

  3. Hands-on experience in laboratory work and is familiar with basic cell and molecular biology techniques

  4. Prior experience in virus handling and analysis, cell culture, mass spectrometry or bioinformatics will be an advantage

  5. Proficiency in written and spoken English

  6. Excellent interpersonal skills, initiative and ability to work independently and in a high-performance team

Number of positions available: 2

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

4. Title: Cellular adaptation to cold (NCN/GRIEG)

Supervisor: Wojciech Pokrzywa, PhD, DSc

Institute: International Institute of Molecular and Cell Biology

Laboratory: Laboratory of Protein Metabolism

Project description:

Environmental stressors can seriously jeopardize animals’ ability to survive and reproduce. One, potentially dangerous, environmental stressor is acute cold. To counteract cold, affected organisms mount various types of responses, ranging from cold avoidance to adaptation.

The latter strategy is used by hibernating animals, which, in extreme cases, can survive subzero temperatures for many days. Here, we propose to utilize a simple animal model, the nematode Caenorhabditis elegans, as a rapid tool to understand cellular adaptations to cold. We will focus on mechanisms altering the abundance and types of cellular messenger RNAs and proteins, as these kinds of molecules are critical for the live-or-die decision of the cell. In some disease states, like stroke, cooling can facilitate patient’s recovery. Moreover, hibernation is of interest to ageing research, as animals tend to live longer at lower temperatures. Thus, understanding how cells adapt to cold has the potential to influence treatments of human disorders.

Aim:

As a Ph.D. student, you will use the powerful genetic model of Caenorhabditis elegans, which can display a hibernation-like behavior, to determine the mechanism and role of the UCS domain-containing proteins and co-working chaperones in the regulation of cross-talk between translation and proteostasis in the cold. To develop the preliminary results, you will use, e.g., polysome profiling, tissue-specific ribosome imaging, RNA sequencing, in vitro assays on purified proteins, and more.

Requirements: 

  1. Holds a master’s degree in biology, biochemistry or related field

  2. Solid knowledge of the principles of cell and molecular biology, genetics, and/or biochemistry

  3. Hands-on experience in laboratory work and familiarity with basic molecular biology techniques

  4. Keen interest in translation and proteostasis regulation 

  5. Prior experience or knowledge of C. elegans or similar model organisms will be an advantage

  6. Proficiency in written and spoken English

  7. Willingness to learn and take new challenges, ability to work independently, analytical thinking

Number of positions available: 1

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

5. Title: Elucidating the epigenetic contribution to cardiovascular lineage specification (NCN/OPUS)

Supervisor: Cecilia Winata, PhD

Institute: International Institute of Molecular and Cell Biology in Warsaw

Laboratory: Laboratory of Zebrafish Developmental Genomics / Zebrafish Developmental Genomics Laboratory

Project description:

One key question in the field of organogenesis relates to how the many types of cells required to make an organ are generated from a pool of progenitor cells with initially similar characteristics. Heart (cardiac) progenitor cells are located close to those that will also generate blood and blood vessels (hemoangiogenic). At very early stages of embryonic development, they express nkx2.5 in common. Subsequently, each type of cells expresses different sets of genes and adopts epigenetic states which signifies their identity. Despite the knowledge that nkx2.5-expressing progenitors could contribute to diverse cell lineage types, several key questions remain unanswered. First, it is unclear at which developmental stage the segregation between cardiac and hemoangiogenic fates begin to occur. Second, the exact pathway and intermediate stages which these progenitors go through during the process of lineage specification are still largely unknown. In addition, despite the knowledge that cardiac transcription factors including Nkx2.5 itself are known to interact with chromatin modifying factors and promote chromatin changes, it is still unknown to what extent epigenetics play a role in driving cell fate decisions at the individual cell level. By tracing the evolution of cellular heterogeneity over time, and at the same time assessing the dynamics of epigenetic landscape at the single cell level, we will elucidate the mechanism of cardiovascular lineage specification.

Aim:

The goal of this project is to elucidate the epigenetic contribution towards the lineage decision of nkx2.5-expressing progenitors into either cardiac or hemoangiogenic lineage. We hypothesize that distinct epigenetic states occur among subpopulations of nkx2.5-expressing progenitors according to their lineage diversification potential. We will profile open chromatin regions at single cell level and determine whether Nkx2.5 plays a role in establishing the epigenetic state by scATAC-seq method (Jia et al., 2018, Nat Commun 9, 4877).

Requirements:

  1. Master’s degree in Biology, Biochemistry, or related area

  2. Solid understanding of the principles of molecular biology and genetics

  3. Previous laboratory experience in molecular biology and/or biochemistry techniques

  4. Prior experience in flow cytometry, NGS, and/or working with animal models (mouse or zebrafish), as well as basic programming skills would be an advantage although not essential

  5. Ability to communicate fluently in English and has a collaborative attitude

Number of positions available: 1

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


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