mgr Paweł Nałęcz-Jawecki |
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Ostatnie publikacje
1. | Grabowski F., Nałęcz‑Jawecki P., Lipniacki T., Predictive power of non-identifiable models, Scientific Reports, ISSN: 2045-2322, DOI: 10.1038/s41598-023-37939-8, Vol.13, No.1, pp.11143-1-12, 2023 Streszczenie: Resolving practical non-identifiability of computational models typically requires either additional data or non-algorithmic model reduction, which frequently results in models containing parameters lacking direct interpretation. Here, instead of reducing models, we explore an alternative, Bayesian approach, and quantify the predictive power of non-identifiable models. We considered an example biochemical signalling cascade model as well as its mechanical analogue. For these models, we demonstrated that by measuring a single variable in response to a properly chosen stimulation protocol, the dimensionality of the parameter space is reduced, which allows for predicting the measured variable’s trajectory in response to different stimulation protocols even if all model parameters remain unidentified. Moreover, one can predict how such a trajectory will transform in the case of a multiplicative change of an arbitrary model parameter. Successive measurements of remaining variables further reduce the dimensionality of the parameter space and enable new predictions. We analysed potential pitfalls of the proposed approach that can arise when the investigated model is oversimplified, incorrect, or when the training protocol is inadequate. The main advantage of the suggested iterative approach is that the predictive power of the model can be assessed and practically utilised at each step. Afiliacje autorów:
| 140p. | |||||||||||||||||||||||||
2. | Nałęcz-Jawecki P., Gagliardi Paolo A.♦, Kochańczyk M.R., Dessauges C.♦, Pertz O.♦, Lipniacki T., The MAPK/ERK channel capacity exceeds 6 bit/hour, PLOS COMPUTATIONAL BIOLOGY, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1011155, Vol.19, No.5, pp.e1011155-1-21, 2023 Streszczenie: Living cells utilize signaling pathways to sense, transduce, and process information. As the extracellular stimulation often has rich temporal characteristics which may govern dynamic cellular responses, it is important to quantify the rate of information flow through the signaling pathways. In this study, we used an epithelial cell line expressing a light-activatable FGF receptor and an ERK activity reporter to assess the ability of the MAPK/ERK pathway to transduce signal encoded in a sequence of pulses. By stimulating the cells with random light pulse trains, we demonstrated that the MAPK/ERK channel capacity is at least 6 bits per hour. The input reconstruction algorithm detects the light pulses with 1-min accuracy 5 min after their occurrence. The high information transmission rate may enable the pathway to coordinate multiple processes including cell movement and respond to rapidly varying stimuli such as chemoattracting gradients created by other cells. Afiliacje autorów:
| 140p. | |||||||||||||||||||||||||
3. | Białecki S., Nałęcz-Jawecki P., Kaźmierczak B., Lipniacki T., Traveling and standing fronts on curved surfaces, PHYSICA D-NONLINEAR PHENOMENA, ISSN: 0167-2789, DOI: 10.1016/j.physd.2019.132215, Vol.401, pp.132215-1-8, 2020 Streszczenie: We analyze heteroclinic traveling waves propagating on two dimensional manifolds to show that the geometric modification of the front velocity is proportional to the geodesic curvature of the frontline. As a result, on surfaces of concave domains, stable standing fronts can be formed on lines of constant geodesic curvature. These lines minimize the geometric functional describing the system's energy, consisting of terms proportional to the front line-length and to the inclosed surface area. Front stabilization at portions of surface with negative Gaussian curvature, provides a mechanismof pattern formation. In contrast to the mechanism associated with the Turing instability, the proposed mechanism requires only a single scalar bistable reaction–diffusion equation and connects the intrinsic surface geometry with the arising pattern. By considering a system of equations modeling boundary-volume interactions, we show that polarization of the boundary may induce a corresponding polarization in the volume. Słowa kluczowe: heteroclinic traveling waves, standing fronts, geodesic curvature, negative Gaussian curvature, domain polarization, pattern formation Afiliacje autorów:
| 100p. | |||||||||||||||||||||||||
4. | 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. | |||||||||||||||||||||||||
5. | Nałęcz-Jawecki P.♦, Szymańska P.♦, Kochańczyk M., Miękisz J.♦, Lipniacki T., Effective reaction rates for diffusion-limited reaction cycles, JOURNAL OF CHEMICAL PHYSICS, ISSN: 0021-9606, DOI: 10.1063/1.4936131, Vol.143, No.21, pp.215102-1-12, 2015 Streszczenie: Biological signals in cells are transmitted with the use of reaction cycles, such as the phosphorylation-dephosphorylation cycle, in which substrate is modified by antagonistic enzymes. An appreciable share of such reactions takes place in crowded environments of two-dimensional structures, such as plasma membrane or intracellular membranes, and is expected to be diffusion-controlled. In this work, starting from the microscopic bimolecular reaction rate constants and using estimates of the mean first-passage time for an enzyme–substrate encounter, we derive diffusion-dependent effective macroscopic reaction rate coefficients (EMRRC) for a generic reaction cycle. Each EMRRC was found to be half of the harmonic average of the microscopic rate constant (phosphorylation c or dephosphorylation d), and the effective (crowding-dependent) motility divided by a slowly decreasing logarithmic function of the sum of the enzyme concentrations. This implies that when c and d differ, the two EMRRCs scale differently with the motility, rendering the steady-state fraction of phosphorylated substrate molecules diffusion-dependent. Analytical predictions are verified using kinetic Monte Carlo simulations on the two-dimensional triangular lattice at the single-molecule resolution. It is demonstrated that the proposed formulas estimate the steady-state concentrations and effective reaction rates for different sets of microscopic reaction rates and concentrations of reactants, including a non-trivial example where with increasing diffusivity the fraction of phosphorylated substrate molecules changes from 10% to 90%. Słowa kluczowe: Enzymes, Enzyme kinetics, Diffusion, Reaction rate constants, Membrane biochemistry Afiliacje autorów:
| 35p. |