The 2016 commission is to create a new work in response to Paul Beales’ and Barbara Ciani’s research on compartmentalisation in biology.
Paul and Barbara have put together a brief outline of their research, and they and their post-doctoral students are happy to answer questions by email, phone or if you’d like to call in for a quick chat.
The Role of Compartmentalisation in Biology
Living organisms are highly sophisticated chemical systems that perform an extraordinary range of elaborate functions. There are no unique physical laws that differentiate the behaviour of animate, living matter such as birds, fish, plants, yeast and bacteria from inanimate objects such as rocks, cars, or a bar of soap.
One of the most important structural properties of living organisms that permits the intricacy and complexity of their behaviour is their division into a hierarchy of compartments. These compartments are defined spatial regions within the organism that contain a distinct set of molecules to perform a specific function. These functional compartments then communicate with each other to direct behaviour at the level of the whole organism.
This organisational complexity occurs across multiple length scales. For example, a human can be divided into functional organs such as the heart, lungs and kidneys. Smaller still, these organs consist of different tissues composed of communicating colonies of cells. Within each cell, the function is divided between different organelles that contribute to its overall behaviour: energy required to function is generated in the structures called mitochondria, blueprints of how it is constructed are contained within a nucleus, new materials required for growth and repair are made in the endoplasmic reticulum, and so on.
The biological cell is often considered to be the fundamental building block of life. The simplest forms of life consist of a single cell. Modern science has developed methods to manipulate cells to become chemical factories to produce materials for human benefit, such as medicines and fuels. This field, called synthetic biology, is still in its infancy and has the potential to engineer biology to perform a great number of tasks for human benefit. There is also a strong drive to be able to build synthetic cells or cell-like materials from their molecular constituents to give a greater degree of control over their structure and function. This is the starting point for the motivation of our research.
Our research project
Our goal is to mimic the compartmentalised structure of the cell by taking the constituent molecules and directing their assembly from the bottom up. Cellular compartments are bound by membranes made up of two back-to-back layers (a bilayer) of fatty molecules called lipids. A large spherical membrane shell (called a vesicle) consisting of a lipid bilayer is the first step in the construction of our artificial cell.
We then use a serious of molecular machines (proteins) that can generate and repair membrane compartments in cells to generate smaller membrane-bound structures within our initial giant membrane shell. We aim to encapsulate different chemistries within these different membrane compartments and engineer communication between these compartments, mimicking how biological cells function.
Cartoon illustrating how the proteins generate new compartments (ILVs) in vesicles:
Image showing confocal microscopy image of ILVs formed within one of our vesicles, encapsulating external cargo and a cartoon illustrating the aim of multiple different reaction compartments within an artificial cell: