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We seek a highly motivated and enthusiastic Postdoctoral Researcher at the Institute of Physical Chemistry, Polish Academy of Sciences. The position is part of the project entitled “Spatial Determinants of Immunotherapy Resistance in Cancer”, funded by the NCN (National Science Centre) in cooperation with the SNSF (Swiss National Science Foundation). Our laboratory at IPC PAS/ICTER provides an international and interdisciplinary research environment with close links to genomics, single-cell sequencing, molecular biology, biotechnology, and bioinformatics. The project involves multimodal (transcriptomic and epigenomic) and spatial profiling of tumor infiltrating immune cells using in-house high-throughput single-cell sequencing methods.

Details about the project:

Significant work over the last two decades has increased our understanding of the intricate, and sometimes opposing roles, that the immune system plays in cancer. While robust immune responses are required for sustained protective anti-tumor responses, tumor infiltrating CD8+ T cells which have the potential to control tumor growth, often acquire a dysfunctional state due to chronic antigen exposure in a nutrient depleted, and suppressive tumor microenvironment (TME). T cell dysfunction is characterized by a gradual loss of effector function coupled with increased expression of immune checkpoint receptors, including CTLA4, PD-1, Lag3 and Tim-3. As a consequence, immune-checkpoint therapy (ICI), using 

blocking antibodies against these receptors, has emerged as an important treatment modality for cancer. ICI has demonstrated unprecedented responses in patients with several types of metastatic tumors that were otherwise refractory to available treatment options. However recent studies show that across all indications only ~13% of patients respond to immunotherapy.

To date, the majority of efforts to understand how cancer immunotherapy restores anti-tumor T cell responses have concentrated on assessing the reactivation of dysfunctional T cells. It was largely thought that the efficacy of checkpoint blockade is mediated by the direct ability of blocking antibodies to bind to co-inhibitory molecules and reverse the state of T cell dysfunction. However, this concept has been challenged with seminal work demonstrating that existing intra-tumoral CD8+ T cells have limited capacity for rejuvenation with a relatively inflexible chromatin landscape, suggesting that the protective effect of ICI is unlikely to be due to reprogramming of dysfunctional T cells. Without a basic understanding of how ICI precisely works we cannot begin to understand why then, in the majority of patients, ICI fails. As such there is great interest in understanding ways to target other immune cells.

To address these questions, we have outlined a series of experiments to analyze the cellular and transcriptional changes associated with tumor infiltrating immune cells. This proposal is highly interdisciplinary implementing single-cell 'omics' strategies and systems immunology approaches to further unravel the players and rules governing immune responses during malignancy. In addition, we plan to develop a suite of computational tools that will allow us to better understand the organization of tumor microenvironment in terms of the cellular composition, spatial arrangement of cells and their communication.

About the group: The Computational Genomics Group at IPC PAS led by dr Marcin Tabaka leverages experimental and computational approaches in high-throughput single-cell transcriptome and epigenome profiling to address fundamental questions in biomedical research (https://tabaka-lab.org).

• Designing, executing, analyzing, and interpreting experiments including high throughput single-cell multimodal profiling
• Assessing quality controls of Next Generation Sequencing data generated in the project
• Optimization of protocols for multimodal analyses (RNA-seq, ATAC-seq) of single cells
• Prepare and write scientific papers for leading journals

• 36-month full-time work contract, not exceeding 2028-03-31
• Engagement into an ambitious research program and opportunity to build an academic career.

The job in the exciting interdisciplinary project. The successful candidate will be able to take advantage of all programs in the IPC PAS, including Young Scientists of IPC PAS competition and Mobility of Young Scientists of IPC PAS competition. The Institute provides an opportunity to participate in ERASMUS+ program.

• Ph.D. degree in Biotechnology, Biology, Genomics, Medicine or related quantitative discipline obtained not earlier than 7 years before the engagement in the project (this period might be longer due to family reasons according to NCN rules).
• Solid knowledge and familiarity with techniques in Genomics
• Familiarity with Next Generation Sequencing
• Familiarity with single-cell methods in Genomics

The Commission will take into account the following criteria and evaluate applications on a point scale:

• Competence for specific tasks in a research project
• Previous scientific achievements (publication record)
• References
• Candidate’s own initiative in research projects.