We are pleased to announce that Prof. Paweł Paszek from the Laboratory of Modelling in Biology and Medicine at IPPT PAN has been awarded an OPUS-29 grant by the National Science Centre (NCN), Poland. The project will investigate how cell-to-cell variability in immune responses contributes to effective antibacterial defence.
Regulation of cellular heterogeneity as an antibacterial control mechanism of infection
Immune responses to bacterial pathogens are inherently heterogeneous: even genetically identical immune cells exposed to the same pathogen can behave very differently. Traditionally, this variability has been viewed as undesirable biological “noise.” However, increasing evidence suggests that cellular heterogeneity itself represents a regulated and functionally important layer of host defence.
Our recent work indicates that major food-borne bacterial pathogens, such as Listeria monocytogenes and Salmonella, actively suppress variability in the expression of key antibacterial effector genes in macrophages. In contrast, conditions that promote heterogeneous immune responses—such as increased cell density—may enhance host resistance. These observations motivate the central hypothesis of the project: that immune heterogeneity is not merely tolerated but actively shapes infection outcomes.
The project will be carried out by a consortium between IPPT PAN and the Nencki Institute of Experimental Biology, PAN. At IPPT PAN, the research will be conducted in the Laboratory of Modelling in Biology and Medicine, which provides access to fully equipped biosafety level-2 laboratories and advanced microscopy platforms enabling high-resolution single-cell analysis of host–pathogen interactions. The Nencki Institute will contribute cutting-edge genomics infrastructure, including expertise in transcriptomics, epigenomics, and single-cell sequencing.
The research team will be led by Prof. Paweł Paszek, in collaboration with Dr hab. Bartosz Wojtaś, Prof. Nencki Institute, Head of the Laboratory of Sequencing at the Nencki Institute.
This interdisciplinary project will integrate single-cell genomics (scRNA-seq, scATAC-seq, and multiome approaches), live-cell imaging and mathematical modelling to dissect how variability in immune signalling and gene expression influences bacterial survival at the single-cell level. Experiments will be performed in macrophage infection models and validated in mouse systems, with a particular focus on tissue-level infection dynamics.
By combining quantitative modelling with high-resolution single-cell experimental data, the project aims to establish a new conceptual framework for innate immunity, in which cellular heterogeneity is viewed as a regulated and exploitable mechanism of host defence. In the longer term, these insights may inform novel antimicrobial strategies that leverage immune diversity rather than attempting to suppress it.
