Elke Deuerling, professor of biochemistry at the University of Konstanz, does what can be called true basic research: her work is focused on finding out more about how new proteins are synthesised and how the quality control of such proteins works.
To understand what Elke Deuerling does is to enter a new dimension containing the tiny structures and building blocks that make up all living organisms along with proteins that carry out vital functions and rapid processes that take no more than a couple of seconds. Welcome to the world of molecular biology. Deuerling is a highly successful molecular biologist and one of the leaders in her field of research. Her laboratory is located on the 10th floor of building M at the University of Konstanz.
Deuerling's task is to search for ordered structures and mechanisms in what she calls the "molecular turmoil of cells". "Cells build proteins using tiny but powerful machines that are known as ribosomes in which amino acids are connected one by one, forming long polypeptide chains. The newly synthesised polypeptide chains are extremely complex and each has a unique composition. Different polypeptide chains have different functions and are folded into a precise three-dimensional structure in a process known as protein folding," explains Deuerling.
The information encoded in genes determines the correct composition of the polypeptide chain. However, in order to carry out specific functions, the amino acid chains need to be correctly folded, a process which is controlled by a complex network of molecular chaperones. In addition to guaranteeing that newly synthesised proteins are folded correctly as they come off the ribosomes, the chaperones can also restore the proper function of misfolded proteins.
However, cells are exposed to a broad range of different hazards. Stress and the ageing of cells might overstrain the chaperones' control system, which can have severe consequences and potentially lead to the development of neurodegenerative diseases, the loss of form and function of proteins, which can aggregate into detrimental clumps and initiate cell death (apoptosis), causing diseases such as Alzheimer's or Parkinson's.
Deuerling and her team's basic research initially focused on simple organisms such as Escherichia coli bacteria and baker's yeast and was then extended to include more complex organisms such as the roundworm Caenorhabditis elegans. This nematode is only about 1 mm long and cannot be seen on a transparent dish Deuerling is holding up to the light. The tiny organism can only be seen under the microscope. C. elegans worms with defective chaperones provide the researchers with important information about basic issues.
Given that the researchers are working on a fairly complex topic, the laboratories are nothing to write home about: they are equipped with instruments such as microscopes, long rows of transparent liquids, incubators and analytical apparatus. The researchers' daily routine involves making the invisible visible. They determine the chemical and physical characteristics of the tiniest molecular structures using nuclear magnetic resonance spectroscopy, fluorescence measurements and many biochemical analysis methods. The investigation of the molecular structures provides them with in-depth insights into the function of cellular proteins. All cells contain a large number of different chaperones that are tethered to ribosomes and interact with nascent polypeptide chains. One of these chaperones is known as the trigger factor and is found in all eukaryotic cells. Elke Deuerling has already published numerous papers about this protein and been awarded several science prizes. Competition in the field of science is enormous, which is why she also works closely with colleagues around the world. She has just prepared a research funding application with colleagues from the elite American university in Stanford.
For Deuerling and her team, the journey into the interior of cells is far from being an end in itself. Once they understand how chaperones ensure the correct protein and cell function, the researchers will at some stage be able to understand how diseases develop and eventually how they can be treated. Deuerling: "I am specifically focused on basic research and I believe that our findings can contribute to obtaining in-depth insights into the processes of ageing and disease development."