PhD in Immunotherapy & 3D Tumor Models – IMol, Polish Academy of Sciences Full-time

The International Institute of Molecular Mechanisms and Machines (IMol) Polish Academy of Sciences, is a new and vibrant institute constituted in partnership with University Medical Center Göttingen, Germany and University of Warsaw, Poland. We provide innovative training, guidance and mentoring in an international “open door” environment with state-of-the-art infrastructure.

Short description of the project

The TUNIC project aims to better understand how neutrophils, the most abundant type of white blood cell, impact cancer immunotherapy. Immunotherapies like immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment, but resistance remains a challenge. The TUNIC project will investigate whether neutrophils can be targeted to enhance immunotherapy efficacy.

Current research on neutrophil function in cancer relies heavily on mouse models, which may not accurately reflect human biology due to significant species-specific differences in neutrophil biology. For example, human neutrophils contain antimicrobial proteins that are absent in mouse neutrophils. Reliance on mouse models has resulted in several failed clinical interventions for human diseases. Similarly, large-scale sequencing datasets, while informative, do not fully elucidate human neutrophil functionality. To overcome these limitations, the TUNIC project will utilize a “phenotype-first” approach. This involves:

• Creating a 3D “tumor-on-a-chip” (ToC) model: This model will incorporate primary human cells, including neutrophils, tumor cells, CD8+ T-cells, and cancer-associated fibroblasts, within a biomimetic 3D hydrogel that replicates the tumor microenvironment.
• Observing neutrophil behaviour: Automated image analysis algorithms will be used to assess how different neutrophil subpopulations directly and indirectly kill tumour cells, and how this behaviour is influenced by other cells in the tumor microenvironment.
• Analysing successful phenotypes: Once a neutrophil subtype with promising anti-tumor activity is identified, advanced bioinformatics-based techniques (sequencing, etc) will be employed to analyse the phenotype within ToC and other 3D models and pinpoint the functional pathways responsible for the observed phenotype.

The TUNIC project expects to identify novel therapeutic targets in neutrophils to boost immunotherapy efficacy in a clinically relevant setting. This research could pave the way for new treatment strategies that overcome immunotherapy resistance in cancer patients.

A bit about the group

At the Laboratory of Advanced Tumor Systems, we combine novel three-dimensional tumor models with primary tumor-derived cells to investigate the therapy-modulating behavior of hard-to-model cell types, such as human neutrophils. Using physiologically relevant systems, we also aim to examine the complex cellular interactions within the tumor microenvironment (TME), with the with the end goal of leveraging these insights to identify novel therapeutic targets for cancer.

Description of the tasks of the project

The Ph.D. student enrolled in this project will collaborate closely with the PI on wet-lab experiments critical to the successful implementation of the project. An example list of potential tasks carried out by the doctoral student over the course of his or her PhD can be seen below:

• Preparation and phenotypic assessment of 3D tumor models using primary cells.
• Phenotype validation using antibody inhibitors, siRNA, shRNA, and other genetic or pharmacological tools.
• Establishment and maintenance of primary and induced pluripotent stem cell (iPSC) cultures derived from peripheral blood mononuclear cells (PBMCs).
• Isolation of primary cell populations from solid tumor tissues and blood.
• Genetic inhibition of target pathways in PBMC-derived iPSCs and differentiation of these cells into neutrophils.

During the initial phases of the project, the PI will lead most of these tasks while training the Ph.D. student in the required techniques. As the project progresses, the Ph.D. student is expected to gain proficiency and gradually achieve independence in performing these tasks.

List of specific requirements

• Master’s degree in Cell Biology, Molecular Biology, Biotechnology, or a related field
• Experience with cell culture, including primary cells and stem cells
• Prior experience with induced pluripotent stem cells (iPSCs), including with differentiation protocols, is considered advantageous
• Familiarity with genetic inhibition techniques such as siRNA, shRNA, or CRISPR
• Proficiency in standard molecular biology techniques (e.g., PCR, Western blotting, immunostaining)
• Strong organizational and time management skills
• Effective communication skills, with proficiency in both spoken and written English
• Collaborative and team-oriented, with a strong willingness to learn

We offer

• Fully funded PhD position;
• Competitive salary 5.000 PLN net/month;
• Work in an active team in an excellent scientific environment;
• Access to the state-of-the-art equipment and facilities;
• Participation in courses and conferences;
• Comprehensive training in biochemistry, cell and molecular biology techniques;

How to apply

Please prepare the following documents (you will be asked to submit the documents merged into one PDF file while filling out the application):

• Motivation letter;
• CV;
• A list of publications and conferences attended;
• Contact details of previous supervisors for reference (please do not attach generic reference letters, but contact details instead).

To apply for this position, please visit the Google Forms link attached to this job offer and select the position labelled as “PhD student – SONATA 20 – Dr Martin Nurmik group” during your application process.

Tagged as: Life Sciences