Learning in single cells through dynamical internal representations

Introduction

Cells continuously sense and interpret the external signals coming from their time-varying environments to generate context-dependent responses. This is true for the entire tree of life, ranging from bacteria and unicellular eukaryotes to neurons forming networks in the developing brain.

Fundamental Questions in Biology

Identifying the fundamental principles and underlying mechanisms that enable cells to interpret their complex natural surroundings and adequately respond remains one of the fundamental questions in biology. Conceptual views so far have been mainly guided by molecular biology descriptions, suggesting that cells are controlled by a genomic program executing a pre-scripted plan.

Alternative Conceptual Framework

Our goal is to develop an alternative conceptual framework:

1. Cells generate internal representations of their external ‘world’.
2. They utilise these representations to actively infer information about it and predict changes.
3. This process determines their response.

Theory of Single-Cell Learning

We will formalise this concept in a theory of single-cell learning by combining:

• Information theory concepts to quantify the predictive information from the internal cell representations.
• Dynamical systems theory to explain how these encodings are realised.

Experimental Approach

We will interrogate experimentally systems across all scales of biological organization:

• Bacteria (B. subtilis)
• Single-cell organisms (Paramecium, Tetrahymena)
• Neuronal cell culture models

By studying them in a comparative manner, we aim at identifying generic molecular mechanisms through which single-cell learning is realised.

Application to Neuronal Development

The acquired understanding will enable us to address in vivo how single neurons during D. melanogaster development learn to form, stabilize, or eliminate axonal branches, to generate stereotyped synaptic patterning under highly variable conditions.

Unifying Framework

We argue that providing a broader and generic definition of learning will serve as a unifying framework, linking disparate areas and scales of biology, and offering a basis for addressing fundamental biological questions.