Partner: Karolina Tudelska |
Ostatnie publikacje
1. | Czerkies M., Korwek Z., Prus W., Kochańczyk M., Jaruszewicz-Błońska J., Tudelska K.♦, Błoński S., Kimmel M.♦, Brasier A.R.♦, Lipniacki T., Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways, Nature Communications, ISSN: 2041-1723, DOI: 10.1038/s41467-017-02640-8, Vol.9, pp.493-1-14, 2018 Streszczenie: The innate immune system processes pathogen-induced signals into cell fate decisions. How information is turned to decision remains unknown. By combining stochastic mathematical modelling and experimentation, we demonstrate that feedback interactions between the IRF3, NF-κB and STAT pathways lead to switch-like responses to a viral analogue, poly(I:C), in contrast to pulse-like responses to bacterial LPS. Poly(I:C) activates both IRF3 and NF-κB, a requirement for induction of IFNβ expression. Autocrine IFNβ initiates a JAK/STAT-mediated positive-feedback stabilising nuclear IRF3 and NF-κB in first responder cells. Paracrine IFNβ, in turn, sensitises second responder cells through a JAK/STAT-mediated positive feedforward pathway that upregulates the positive-feedback components: RIG-I, PKR and OAS1A. In these sensitised cells, the 'live-or-die' decision phase following poly(I:C) exposure is shorter—they rapidly produce antiviral responses and commit to apoptosis. The interlinked positive feedback and feedforward signalling is key for coordinating cell fate decisions in cellular populations restricting pathogen spread. Słowa kluczowe: cellular signalling networks, innate immunity, regulatory networks, stochastic modelling Afiliacje autorów:
| 45p. | |||||||||||||||||||||||||||||||
2. | Tudelska K.♦, Markiewicz J., Kochańczyk M., Czerkies M., Prus W., Korwek Z., Abdi A.♦, Błoński S., Kaźmierczak B., Lipniacki T., Information processing in the NF-κB pathway, Scientific Reports, ISSN: 2045-2322, DOI: 10.1038/s41598-017-16166-y, Vol.7, pp.15926-1-14, 2017 Streszczenie: The NF-κB pathway is known to transmit merely 1 bit of information about stimulus level. We combined experimentation with mathematical modeling to elucidate how information about TNF concentration is turned into a binary decision. Using Kolmogorov-Smirnov distance, we quantified the cell's ability to discern 8 TNF concentrations at each step of the NF-κB pathway, to find that input discernibility decreases as signal propagates along the pathway. Discernibility of low TNF concentrations is restricted by noise at the TNF receptor level, whereas discernibility of high TNF concentrations it is restricted by saturation/depletion of downstream signaling components. Consequently, signal discernibility is highest between 0.03 and 1 ng/ml TNF. Simultaneous exposure to TNF or LPS and a translation inhibitor, cycloheximide, leads to prolonged NF-κB activation and a marked increase of transcript levels of NF-κB inhibitors, IκBα and A20. The impact of cycloheximide becomes apparent after the first peak of nuclear NF-κB translocation, meaning that the NF-κB network not only relays 1 bit of information to coordinate the all-or-nothing expression of early genes, but also over a longer time course integrates information about other stimuli. The NF-κB system should be thus perceived as a feedback-controlled decision-making module rather than a simple information transmission channel. Słowa kluczowe: cellular signaling networks, innate immunity, stress signaling Afiliacje autorów:
| 40p. | |||||||||||||||||||||||||||||||
3. | Korwek Z., Tudelska K.♦, Nałęcz-Jawecki P.♦, Czerkies M., Prus W., Markiewicz J., Kochańczyk M., Lipniacki T., Importins promote high-frequency NF-κB oscillations increasing information channel capacity, Biology Direct, ISSN: 1745-6150, DOI: 10.1186/s13062-016-0164-z, Vol.11, No.61, pp.1-21, 2016 Streszczenie: BACKGROUND: Słowa kluczowe: Karyopherins, Nucleocytoplasmic transport, Negative feedback, Channel information capacity, Mathematical modelling Afiliacje autorów:
| 35p. |