When can synthetic division be used

Synthetic microbiology

For synthetic microbiology, scientists study the processes in microorganisms in order to then change the design of the cells so that they produce chemicals for industry or medicinal substances, for example. Lisa Leander spoke for the podcast with Bruno Eckhardt from the University of Marburg about metabolic pathways on the micrometer scale and the special behavior of cell colonies. Here you can find the article for reading.

Microorganisms usually only consist of individual cells, but today they are of great importance in industry, for example in the production of pharmaceuticals or in biotechnology. In order to be able to use the cells, researchers have to understand fundamentally how they divide, how their metabolism works and which biochemical signals they can send out, which in turn affect other cells. Synthetic microbiology has set itself the goal of examining these processes, changing them and, in a final step, artificially producing cells with new properties. To this end, scientists from many areas work together, including physicists. Because not only the microscope techniques used to examine cells are based on physical principles. Often times, physicists help describe the organisms themselves.

Bruno Eckhardt

Bruno Eckhardt: In these microorganisms, the chemical constituents, the proteins, are not always present in the quantities that they can be described by continuous comparisons and that the mode of action is as direct and efficient as is described in the lock-and-key principles of biology. You have to expect that processes will run with errors or that fluctuations will occur. The description of fluctuations is one of the basic elements of statistical physics, which means that statistical physics methods also come into play.

The study of organisms becomes even more difficult when you consider that the distribution of proteins in the cell changes frequently. Scientists call these fluctuations oscillation.

One observes that the proteins are only localized at one cell pole and after a while they collect at the other cell pole - and then return again. This change from cell pole to cell pole is relatively regular and associated with a relatively easily identifiable periodicity. There are examples in which researchers have simulated the whole thing in vitro, and one finds the same spatiotemporal patterns that are known from other pattern-forming chemical reactions. The particular charm of biological systems is that they are linked to the functions of the cell - and the challenge is to identify the molecular players involved.

One of the functions with which these processes are related is the division of cells. The migration of the proteins defines the center of the cell and thus the point for division. In addition, microorganisms can change their direction of movement through oscillation. Some bacteria have another means of changing direction and locomotion: the flagella. They consist of protein threads or protuberances of the cell and can appear individually or as a bundle.

Cell division

These flagella are driven by a motor, which is essentially constructed like an electric motor and is driven by a flow of protons. The motor sets the thread-like flagella in rotation and this rotation causes the bacteria to move.

After understanding the molecular structure, researchers in synthetic microbiology move on to varying the structure of the flagella.

You can make them longer, you can make them shorter, or you can change their number, thereby enabling the bacteria to move faster, slower or differently. We are investigating how this affects the currents around the bacteria, what happens when several of them come together, and how the interaction of many bacteria in these colonies works.

When bacteria or other organisms begin to move together to form such colonies, they behave differently than when they could still move freely.

Bacteria with flagella

Then there is differentiation in the individual cells, some of which shed their flagella, which begin to release extracellular polymers with which the cells then move together, stick together and form a biofilm. A division of labor can also be observed in this biofilm: the cells further inside take on different functions than those on the surfaces.

Biofilms can be very annoying, for example on prostheses inside the human body or on food. Eckhardt and his colleagues are trying to figure out the mechanisms by which biofilms work, so that, for example, their formation can be prevented. On the other hand, biofilms give a fascinating insight into the self-organization of cells.

Another organism that has been studied in this context and that is fascinating is a green alga called Volvox. As a single algae or in groups of a few algae, it forms a compact ball. However, when the number of algae becomes very large, they begin to form a hollow body. The transition can be made plausible by considering energy and supply balances, which are easier and cheaper for this hollow body with the large surface and direct access to the organisms than for a compact organism, where the cells inside are only supplied with difficulty can be.

Cell colonies of the green alga Volvox as hollow bodies

In addition to the targeted modification of existing cells, the researchers are also concerned with the construction of so-called minimal organisms. A functioning cell should be constructed purely synthetically and from as few components as possible. If the minimal organisms are then further developed, they could be of great practical use.

If you understand the metabolic pathways well enough, you can convince cells to make products that they would not make under normal conditions. This can be used to specifically manufacture biotechnologically relevant products in host organisms - from antibiotics to antibodies to fine chemicals for white biotechnology.

One goal of the scientists is to create biological modules with which cells with the desired properties can be constructed according to a kind of modular principle. They could form the basis for new technologies that industry uses to produce new drugs, chemicals or biofuels. Minimal organisms can also be of interest for the fundamental question of how simply structured cells developed as the first forms of life on earth. In this way, the understanding and design of cell functions are closely intertwined so that scientists on the one hand get to know the natural potential of microorganisms and on the other hand can fully exploit it.