Hidden states and currents in biological systems

Introduction

The ability to infer information about hidden degrees of freedom from time series would revolutionize experiments on single molecules, mesoscale assemblies, and tissues, as well as financial and climate systems. Hidden dynamics are often essential, as they reflect the approaching of a critical transition or describe its mechanism, e.g., the folding of a protein or RNA, or an abrupt shift in climate.

Project Goals

With the project proposed here, I plan to push our quantitative understanding of experiments, ranging from single-molecule spectroscopy to observations of migrating cells and developing tissues, to a new level. This will be achieved by exploiting how the properties of a high-dimensional landscape and current imprint onto the time ordering of projected states along individual trajectories.

Methodology

I will introduce functionals of projected paths that are easily inferred from data and analyze their statistics and measure concentration by combining:

1. The theory of functionals of stochastic paths
2. Concentration inequalities
3. Semiclassical analysis

These methods will be applied to:

• Single-molecule force spectroscopy
• Plasmon ruler experiments
• Cell tracking
• Molecular Dynamics simulations

Distinctive Characteristics

A distinctive characteristic of the project is the focus on non-asymptotic measure concentration, i.e., on “occurs with high probability” results that will be addressed for the first time in the context of non-equilibrium physics.

Expected Outcomes

Providing a new framework for interpreting experiments—using the information readily encoded in the data but inaccessible to existing approaches—the project will generate new knowledge that will:

• Resolve the long-standing debate about intermediates in DNA, RNA, and protein folding
• Address controversies about non-converging dynamics of folded proteins
• Shed new light on the operation of nanomachines and self-assembly far from equilibrium
• Illuminate cell movements during tissue regeneration

Impact

This project will lead to a paradigm shift in soft matter and biophysics and may reshape actuarial and climate science.