mgr Tomasz Jetka


Ostatnie publikacje
1.Jetka T., Nienałtowski K., Filippi S., Stumpf M.P.H., Komorowski M., An information-theoretic framework for deciphering pleiotropic and noisy biochemical signaling, Nature Communications, ISSN: 2041-1723, DOI: 10.1038/s41467-018-07085-1, Vol.9, pp.4591-1-9, 2018

Streszczenie:

Many components of signaling pathways are functionally pleiotropic, and signaling responses are marked with substantial cell-to-cell heterogeneity. Therefore, biochemical descriptions of signaling require quantitative support to explain how complex stimuli (inputs) are encoded in distinct activities of pathways effectors (outputs). A unique perspective of information theory cannot be fully utilized due to lack of modeling tools that account for the complexity of biochemical signaling, specifically for multiple inputs and outputs. Here, we develop a modeling framework of information theory that allows for efficient analysis of models with multiple inputs and outputs; accounts for temporal dynamics of signaling; enables analysis of how signals flow through shared network components; and is not restricted by limited variability of responses. The framework allows us to explain how identity and quantity of type I and type III interferon variants could be recognized by cells despite activating the same signaling effectors.

Afiliacje autorów:

Jetka T.-IPPT PAN
Nienałtowski K.-IPPT PAN
Filippi S.-Imperial College London (GB)
Stumpf M.P.H.-Imperial College London (GB)
Komorowski M.-IPPT PAN
45p.
2.Aliper A.M., Csoka A.B., Buzdin A., Jetka T., Roumiantsev S., Moskalev A., Zhavoronkov A., Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells, Aging-US, ISSN: 1945-4589, Vol.7, No.1, pp.26-37, 2015

Streszczenie:

For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson‐Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle‐age, and old‐age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle‐aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

Słowa kluczowe:

Progeria, HGPS, Lamin, LMNA, aging, aging pathway, pathway activation, pathway drift, geroscope, geroprotectors, senescence

Afiliacje autorów:

Aliper A.M.-Johns Hopkins University (US)
Csoka A.B.-Howard University (US)
Buzdin A.-Johns Hopkins University (US)
Jetka T.-IPPT PAN
Roumiantsev S.-Johns Hopkins University (US)
Moskalev A.-Johns Hopkins University (US)
Zhavoronkov A.-Johns Hopkins University (US)
30p.
3.Jetka T., Charzyńska A., Gambin A., Stumpf M.P.H., Komorowski M., StochDecomp—Matlab package for noise decomposition in stochastic biochemical systems, BIOINFORMATICS, ISSN: 1367-4803, DOI: 10.1093/bioinformatics/btt631, Vol.30, No.1, pp.137-138, 2014

Streszczenie:

Motivation: Stochasticity is an indispensable aspect of biochemical processes at the cellular level. Studies on how the noise enters and propagates in biochemical systems provided us with non-trivial insights into the origins of stochasticity, in total, however, they constitute a patchwork of different theoretical analyses.

Results: Here we present a flexible and widely applicable noise decomposition tool that allows us to calculate contributions of individual reactions to the total variability of a system’s output. With the package it is, therefore, possible to quantify how the noise enters and propagates in biochemical systems. We also demonstrate and exemplify using the JAK-STAT signalling pathway that the noise contributions resulting from individual reactions can be inferred from data experimental data along with Bayesian parameter inference. The method is based on the linear noise approximation, which is assumed to provide a reasonable representation of analyzed systems.

Afiliacje autorów:

Jetka T.-IPPT PAN
Charzyńska A.-University of Warsaw (PL)
Gambin A.-other affiliation
Stumpf M.P.H.-Imperial College London (GB)
Komorowski M.-IPPT PAN
40p.

Lista rozdziałów w ostatnich monografiach
1.
587
Nienałtowski K., Jetka T., Komorowski M., Quantitative Biology. Theory, Computational Methods, and Models, rozdział: Sensitivity analysis, Edited by Brian Munsky, William S. Hlavacek and Lev S. Tsimring, pp.293-319, 2018
2.
588
Jetka T., Nienałtowski K., Komorowski M., Quantitative Biology. Theory, Computational Methods, and Models, rozdział: Experimental design, Edited by Brian Munsky, William S. Hlavacek and Lev S. Tsimring, pp.321-337, 2018

Abstrakty konferencyjne
1.Zakrzewska K.E., Jetka T., Nienałtowski K., Szymańska K., Andryka K., Topolewski P., Głów E., Komorowski M., Sensing and remembering IFNs concentrations, Cytokine, ISSN: 1043-4666, DOI: 10.1016/j.cyto.2017.09.011, No.Mo-P7-12, pp.100, 201725p.
2.Andryka K., Głów E., Nienałtowski K., Jetka T., Komorowski M., Sensing accuracy of interferons' concentrations, Cytokine, ISSN: 1043-4666, DOI: 10.1016/j.cyto.2015.08.238, Vol.76, pp.108, 2015

Streszczenie:

Interferons exhibit their key role of immune modulators through activation of the Jak-Stat signalling pathway. We know substantial amount of molecular details regarding functioning of the pathway. However, to what extend the action of the pathway is dose dependent at the single cell level remains largely unclear. Specifically it is not know if single cells respond in a digital fashion or their output is continuously dependent on the stimulant’s concentration. We have combined an information-theoretic framework with high-throughput confocal imaging of mouse embryonic fibroblasts to provide a thorough, single-cell analysis of the Jak-Stat signalling in response to interferon beta and interferon gamma. We showed that in a baseline state single cells have information hardly sufficient to distinguish between presence or absence of interferons. However they can be put in an alert state by an action of interferons, which allows them to respond more in an analogous fashion. Our results show that the accuracy with which signalling pathways transmit information is not fixed but can be modulated on the contextual basis.

Afiliacje autorów:

Andryka K.-IPPT PAN
Głów E.-IPPT PAN
Nienałtowski K.-IPPT PAN
Jetka T.-IPPT PAN
Komorowski M.-IPPT PAN
25p.
3.Jetka T., Komorowski M., How can we quantify ligand sensitivity for single-cell heterogenous dynamical responses?, FEBS Journal, ISSN: 1742-464X, Vol.281, No.Supplement: 1, Special Issue: SI, pp.625, 2014

Słowa kluczowe:

Information Processing, Sensitivity Analysis, Signal Transduction

Afiliacje autorów:

Jetka T.-IPPT PAN
Komorowski M.-IPPT PAN
4.Głów E., Jetka T., Komorowski M., Sensitisation in the IFN-alpha/b, IFN-gamma crosstalk reveals mechanisms for enhanced information processing capacity of the STAT1, STAT2 signalling pathway, FEBS Journal, ISSN: 1742-464X, Vol.281, No.Supplement: 1, Special Issue: SI, pp.640, 2014

Słowa kluczowe:

Interferon, Jak/Stat, Stimulation

Afiliacje autorów:

Głów E.-IPPT PAN
Jetka T.-IPPT PAN
Komorowski M.-IPPT PAN