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Identification of transcriptional memory maintenance factors through a cell selection strategy

Periodic Reporting for period 1 - IMMUNE-GENEMEMO (Identification of transcriptional memory maintenance factors through a cell selection strategy)

Reporting period: 2021-06-01 to 2023-05-31

Cellular memory of gene expression states is essential for development and maintenance of tissues and hence for human health. How this process is controlled on a molecular level is not fully understood. Here we study the phenomenon of innate immune memory, specifically transcriptional memory, to gain new insights into maintenance mechanisms of gene expression states.
Transcriptional memory is a biological process during which cells induced with a particular signal display increased rates of gene expression after re-stimulation at a later stage. In this project, I use an unbiased genetic strategy to identify novel transcriptional memory regulatory factors to understand the molecular mechanisms of the phenomenon. I next generalize the discovered knowledge to the biology of innate immune cells.
This project empowers me to establish myself as a scientific leader in the field. Insights from this research uncover new gene regulatory mechanisms and pave the way for manipulation of the innate immune system for the benefit of public health.
So far in the project, I managed to perform the genetic screen and identified potential regulatory factors of transcriptional memory. Moreover, I extended the transcriptional memory observation to other cells of the innate immune system e.g. monocytes and macrophages. On top of that, I discovered a specific change in cellular biology that correlates with transcriptional memory and built tools to test the significance of this observation. Finally, I tested the function of a specific protein factor in the memory phenomenon.

Overview of the exploitation and dissemination actions:
So far, in the project I published a paper in an international peer reviewed journal (EMBO journal) and presented the data as an invited speaker at the Harvard Medical School and the University of Gdansk.
I have now gained novel insight into the mechanism of transcriptional memory. I will continue my work to understand how transcriptional memory is established and maintained on the molecular level. I will next generalize the knowledge to biology of innate immune cells with the aim to translate the discoveries to novel immunotherapies. This will result in industrial collaborations, new jobs in the biotechnology sector and most importantly new ways to treat disease.
Transcriptional memory