From Molecules to Systems: Towards an Integrated Heuristic for Understanding the Physics of Life

The last fifty years have seen enormous strides in our understanding of biology at the most basic level, the molecular scale. For example, the structure of DNA has been discovered, and the genetic information encoded in its structure has begun to be worked out. We know that many biological molecules are associated with particular types of behaviour in larger organisms: for example some people have a genetic predisposition to particular diseases. However, understanding the complex links in the chain between a single molecule inside a cell and the behaviour of a person is a very difficult challenge. We can focus in on individual molecules and understand their structures and behaviour in great detail, but every human body contains vast numbers of molecules of many different types, and the challenge is to try to put together the complex systems of interactions between molecules that go on inside each cell; the relationships between cells that lead to the function of tissue; and the way that tissues and organs are integrated into a whole person. When a person discovers they have cancer, for example, there is a strong chance that the disease began with a change in a single molecule; but this will have initiated a staggeringly complex cascade of knock-on chains of cause-and-effect that led to the formation of the disease, and modern epigenetics is also suggesting that a complex chain of cause-and-effect may very well have preceded that initial change. Untangling this web of interactions is an enormous challenge but it is undoubtedly the most important problem facing biology at present.

It is clear that biological systems function on different length scales (molecules/cells/tissues/people) and the challenge is to integrate understanding across the length scales. The ways that biologists think about molecules are very different from the ways that they think about ecosystems, for example, even though a molecular event can trigger a change in an ecosystem. Physics has been addressing the problem of integrating across length scales for many years. At the most extreme, quantum gravity tries to integrate the laws of quantum mechanics (which deals with the smallest building blocks of matter) and general relativity (which describes the behaviour of planets, stars and galaxies). Importantly, physicists have been thinking about detail and also how to integrate across length scales to develop a picture of very large systems. We believe that this gives physicists unique insights that may potentially help biologists to integrate their thinking across the length scales too. The goal of this Network proposal is to stimulate engagement between physicists and biologists to tackle this important challenge together.

The Network will provide a range of activities designed to help physicists and biologists build new partnerships devoted to finding a framework to understand biology across the length scales. Three initial events will focus on key challenges (How do many molecules come together to form a living cell? Can we build synthetic systems that replicate cell behaviour and allow us to understand how the integration from molecules to cells functions? How do many cells work together in tissue, biofilm or other forms?) Following these initial events a series of activities will be developed to provide the means of bringing leading physicists and biologists together to address the important challenges identified.

Our goal will be to provide a framework from within which physicists and biologists can work together to understand biology across the length scales. The rewards for this effort are many, including the development of a better understanding of disease (for example, cancer), ecosystems and the environment, photosynthesis and biological energy harvesting, biotechnology and biofilms. Inevitably this will contribute substantially to the many bioscience-related industries in the UK and to the health and quality of life of its citizens.

Undoubtedly, the most immediate impact of our Network will be upon academic science. However, the science that we aim to address - the integration of understanding across the length scales - is so fundamental that it underpins a great deal of biology. There are many ways in which a better understanding of the connections between molecular processes and systems behaviour may benefit society. The following are simply a small number of illustrations.
(i) Ecosystems are important in agriculture, and in the conservation of our environment. There is good evidence that molecular phenomena may trigger changes in the behaviour of entire ecosystems. Understanding these complex correlations could be critical in many different ways, from understanding the impact of a xenobiotic compound on the viability of sensitive habitats, to understanding the likely effects of genetically modified organisms in the environment.
(ii) Molecular-level changes are known to be important in many diseases. Cancer provides one illustration. Changes in a single molecule may ultimately lead to a cancerous organ and the death of a person. The potential of physicists to address the kind of cross-length-scale challenges involved in tackling a disease like cancer was recently recognised by the US National Science Foundation, and led to the radical move of establishing an NIH-NSF cancer network specifically to harness the expertise of physicists. While cancer is a disease that has a high public profile, it is not unique and many other diseases pose similar cross-length-scale challenges.
(iii) Biofilms are complex systems of multiple interacting cells. They acquire collective forms of behaviour that are not found in isolated cells. Biofilms are of enormous economic and human significance. For example, the colonisation of urinary catheters by bacterial biofilms costs the NHS many millions of pounds every year and causes suffering to many people who subsequently develop urinary tract infections. From the fouling of ship hulls to the bioremediation of contaminated land, there are many ways in which the development of an understanding that spanned the molecular and systems levels of understanding could have major economic benefit to the UK.
These examples illustrate some of the very many ways that impact could be generated by the new framework for understanding biology across the length scales that our NetworkPlus would aim to establish.