Periodic Reporting for period 2 - IMMUNE-GENEMEMO (Identification of transcriptional memory maintenance factors through a cell selection strategy)
Période du rapport: 2023-06-01 au 2024-05-31
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.
In conclusion, in this project we discovered a novel mechanism of transcriptional memory that we published in the EMBO journal. Additionally, by performing a genetic screen we paved the way for future discoveries and translation to a clinical setting. Moreover, we extended the observations to other cell types. Aside from that, we tested several mechanistic hypothesis. In addition, I promoted the results of this action as an invited speaker at Harvard Medical School and the University of Gdansk, but also during two outreach activities that I organized. As a consequence of this action, I was able to secure an associate professor position at the University of Gdansk, together with independent funding to continue this research.
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.
In conclusion, in this project we discovered a novel mechanism of transcriptional memory that we published in the EMBO journal. Additionally, by performing a genetic screen we paved the way for future discoveries and translation to a clinical setting. Moreover, we extended the observations to other cell types. Aside from that, we tested several mechanistic hypothesis. In addition, I promoted the results of this action as an invited speaker at Harvard Medical School and the University of Gdansk, but also during two outreach activities that I organized. As a consequence of this action, I was able to secure an associate professor position at the University of Gdansk, together with independent funding to continue this research.
In the project, I managed to perform the genetic screen and identified potential regulatory factors of transcriptional memory. Next, I validated the observations by a complementary method that I established in my laboratory. Moreover, I extended the transcriptional memory observation to other cells of the innate immune system e.g. monocytes and macrophages as well as primary cells. 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 different specific protein factor in the memory phenomenon.
Overview of the work performed from the beginning to the end of the project per Work package:
Work Package 1: Identification of novel factors controlling maintenance of transcriptional memory and IFNγ signal transduction.
I performed the genetic screen and identified putative activators, repressors and memory regulators of IFNγ stimulation.
Work package 2: Validation and generality of identified mechanisms.
I extended the IFNγ transcriptional memory observation to other cell types. With this, I established a valuable system to generalize the discoveries made during this project.
Work package 3: Dissemination and exploitation of the project results to scientific community and to the public.
We published a manuscript describing a novel mechanisms of transcriptional memory in a high quality, peer-reviewed international journal – the EMBO journal. Additionally, I presented my data in a form of a seminar at Harvard Medical School as well as University of Gdansk. Moreover, I designed and executed two outreach activities with a competition and a prize describing epigenetic processes as well as my research interests.
Work package 4: Project management.
I established an independent laboratory at the University of Gdansk and secured generous funding to continue my research on transcriptional memory. On top, I completed a 9-month long Leadership in Research course offered by Harvard University. Finally, I got promoted to an associate professor at the University of Gdansk.
Overview of the exploitation and dissemination actions:
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. Moreover, I designed and executed two outreach activities with a competition and a prize at the Biologist’s Night and at the EXPERYMENT Science Museum. Finally I disseminated the project results via social media and a dedicated website.
Overview of the work performed from the beginning to the end of the project per Work package:
Work Package 1: Identification of novel factors controlling maintenance of transcriptional memory and IFNγ signal transduction.
I performed the genetic screen and identified putative activators, repressors and memory regulators of IFNγ stimulation.
Work package 2: Validation and generality of identified mechanisms.
I extended the IFNγ transcriptional memory observation to other cell types. With this, I established a valuable system to generalize the discoveries made during this project.
Work package 3: Dissemination and exploitation of the project results to scientific community and to the public.
We published a manuscript describing a novel mechanisms of transcriptional memory in a high quality, peer-reviewed international journal – the EMBO journal. Additionally, I presented my data in a form of a seminar at Harvard Medical School as well as University of Gdansk. Moreover, I designed and executed two outreach activities with a competition and a prize describing epigenetic processes as well as my research interests.
Work package 4: Project management.
I established an independent laboratory at the University of Gdansk and secured generous funding to continue my research on transcriptional memory. On top, I completed a 9-month long Leadership in Research course offered by Harvard University. Finally, I got promoted to an associate professor at the University of Gdansk.
Overview of the exploitation and dissemination actions:
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. Moreover, I designed and executed two outreach activities with a competition and a prize at the Biologist’s Night and at the EXPERYMENT Science Museum. Finally I disseminated the project results via social media and a dedicated website.
In this project we significantly went beyond the state of the art. We discovered a novel function of a key transcription factor STAT1 in establishment of transcriptional memory. On top, we performed a genetic screen and identified several novel, putative regulatory factors of the process.
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.
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.