Periodic Reporting for period 1 - Cellinfo (Quantification of information flow in a cell signaling pathway)
Okres sprawozdawczy: 2022-09-01 do 2024-08-31
Living organisms make decisions based on the information they collect from the environment. Decisions are met on every level of organismal function, including single cells which make up the organism. Cells use signalling pathways as windows into the environment to collect information. Signalling pathways are interconnected cascades of chemical reactions which transduce the information received at the receptor anchored in the cell membrane through a number of phosphorylation hubs. The relayed information is decoded by the cell and used to govern characteristic behaviours: growth, migration, division, apoptosis, etc. One of the key signalling pathways is the mitogen-activated protein kinase MAPK (ERK) pathway, highly conserved in eukaryots and governing multiple cellular functions. This fine-tuning of the MAPK pathway prompted a number of studies aiming to quantify the amount of information it transduces. Surprisinly, the results reported very low information content, ascribing the fine-tuning of the pathway function to other cellular mechanisms.
The main objective of the project is a quantification of the intracellular information flow relayed through the MAPK signalling pathway. This broad objective encompasses several research questions addressed in the project. The first question, directly addressing the conundrum in the field, probes the ability of the pathway to distinguish between stimuli of different strengths, quantified as the number of bits of information relayed. The next step tackles the challenging estimate of the information exchanged between cells without external inputs. Finally, the project assesses the information encoded in the dynamic signal the pathway receives from the environment.
The importance of this research is closely tied to our advancement in understanding of organismal function. In the last decade, the interest in behaviour, decision-making and even cognitive properties on the level of single cells and cell populations has been reignited. The information-processing strategies lie at the heart of the described phenomena, making the efforts to quantify the information, such as in this project, highly relevant.
The main objective of the project is a quantification of the intracellular information flow relayed through the MAPK signalling pathway. This broad objective encompasses several research questions addressed in the project. The first question, directly addressing the conundrum in the field, probes the ability of the pathway to distinguish between stimuli of different strengths, quantified as the number of bits of information relayed. The next step tackles the challenging estimate of the information exchanged between cells without external inputs. Finally, the project assesses the information encoded in the dynamic signal the pathway receives from the environment.
The importance of this research is closely tied to our advancement in understanding of organismal function. In the last decade, the interest in behaviour, decision-making and even cognitive properties on the level of single cells and cell populations has been reignited. The information-processing strategies lie at the heart of the described phenomena, making the efforts to quantify the information, such as in this project, highly relevant.
In this project, the questions about the information flow in the MAPK pathway were revisited by establishing a novel quantification framework based on the feedback between experiments and theory.
The results of the project revealed that the reason behind previous reports of low information content lies in experimental obstacles which seemingly decreased the amount of information. By overcoming these obstacles with experiments using repeated optogenetic stimulations of the MAPK pathway and a robust, single-cell readout of the pathway activity, the measurements showed that the amount of information the MAPK pathway can transduce is much larger than previously thought. Furthermore, the results revealed that the pathway relies on the dynamics of the response signal to encode information. The project delved deeper into the dynamics of ERK activity and its relationship to information content, revealing that the information is indeed encoded in the dynamics of the signal. Finally, the project assessed the natural input levels the cells receive from their environment in the absence of perturbative stimuli, as well as explored the relationship between the spontaneous ERK dynamics and information relayed from external stimulation. The results of this project were continuously disseminated by means of numerous presentations in scientific meetings, discussions and exchanges, and a publicly available manuscript.
The results of the project revealed that the reason behind previous reports of low information content lies in experimental obstacles which seemingly decreased the amount of information. By overcoming these obstacles with experiments using repeated optogenetic stimulations of the MAPK pathway and a robust, single-cell readout of the pathway activity, the measurements showed that the amount of information the MAPK pathway can transduce is much larger than previously thought. Furthermore, the results revealed that the pathway relies on the dynamics of the response signal to encode information. The project delved deeper into the dynamics of ERK activity and its relationship to information content, revealing that the information is indeed encoded in the dynamics of the signal. Finally, the project assessed the natural input levels the cells receive from their environment in the absence of perturbative stimuli, as well as explored the relationship between the spontaneous ERK dynamics and information relayed from external stimulation. The results of this project were continuously disseminated by means of numerous presentations in scientific meetings, discussions and exchanges, and a publicly available manuscript.
By settling the dispute in the research field regarding the amount of information transduced through the MAPK pathway, the results of this project significantly shifted the state of the art on quantification of intracellular information flow. The establishment of a robust and accurate information quantification framework provided a basis for previously inaccessible, yet highly relevant measurements of intracellular information in dynamic settings where information flows likely play a key role, such as during organismal development.