Bright Prospects in Biophysical Chemistry

For the young scientist just starting out in biophysical chemistry the horizon is unlimited. Sybren Wijmenga, a newly appointed professor of biophysical chemistry and head of the laboratory of biophysical chemistry in Nijmegen University in the Netherlands gives a detailed view of both the current situation and the future prospects for biophysical chemistry research in the Netherlands and across Europe.

Standing at the crossroads of physics, chemistry, biology, and the medical sciences, biophysical chemistry is the study of biomolecules by using physical and chemical methods. Therein lies the beauty of this field: It is truly multidisciplinary, requiring skills in molecular biology, biochemistry, bioinformatics, physics, and even the medical sciences, which makes a biophysical chemist a ?universal" scientist.

For young scientists who have an interest in the fundamental aspects of science, but at the same time feel that their work should (when possible) contribute to a better understanding of biology and perhaps even improve life?s quality, biophysical chemistry ought to be an attractive research area. And in this postgenomic era there is plenty of room to make a contribution: For the young scientist just starting out in the field of biophysical chemistry the horizon is unlimited.

The successful completion of the human genome (as well as several others) has fuelled an explosion of activities in new basic sciences that have spin-offs into biotechnology. In this postgenomic era it is becoming more and more important to understand the molecular functions of the genetic material (i.e., DNA, genes, and chromosomes), as well as those of the gene products--whether those products are RNA or protein.

Key questions include ?What is their three-dimensional structure?" ?How do they interact?" and ?Do they have internal motion?" New buzzwords, such as functional and structural genomics, proteomics, ribonomics, or metabolomics, are popping up, each describing, in one way or another, new attempts to study complete biological systems.

As the questions get more complicated, so too do the experimental methodologies. So cutting-edge technologies, such as laser light spectroscopy, electron microscopy, x-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and mass spectroscopy, are all coming to the fore, but need further refinement if they are to be used to find answers to these questions.

The fundamental concepts underpinning the field of biophysical chemistry are crucial for further progress in many related fields of applied research. The spin-offs from our scientific knowledge include defining new drug targets, designing new drugs with high target specificity, developing disease resistant plants, and finally developing new nanotechnologies.

This rapidly expanding field provides excellent job opportunities for young scientists inside and outside academia. Today, nearly every university or research institute has a biophysics or biophysical chemistry laboratory. Apart from the pharmaceutical companies that have structure- or biophysics-oriented research departments, many new biotechnology companies have developed expertise in this area in recent years.

Nijmegen--A Hot Spot for Interdisciplinary Research

In Nijmegen at the laboratory of biophysical chemistry we focus on four main research areas that employ NMR and complement it with other biophysical techniques. NMR is ideally suited for functional studies. It is the only method that can simultaneously provide information on the three-dimensional structure, dynamics, and the interaction of biomolecules in solution--and thus under physiological conditions.

First, we want to understand the molecular and physical events behind protein-misfolding diseases such as Alzheimer?s disease. Second, we are trying to unravel the protein-protein interactions involved in signaling processes. A third area of research involves infectious agents. We are focusing on the hepatitis B virus (HBV) and the human immune deficiency virus (HIV), both of which contribute to global health problems. Our hope is that a better understanding of the structure of the HBV RNA will lead to the development of an effective antiviral drug.

Finally, we are developing methods for the faster determination of nucleic acid structure. When successful, this opens the door to the efficient exploration of the effect of structural changes due to mutations, so that molecular recognition processes can be understood in much greater detail. It will also enable effective drug development based on structural principles and contribute to the field of nanotechnology, where nucleic acids are often used as building blocks and scaffolds.

The Research Landscape

For an interdisciplinary research group such as ours, close ties to other departments and international collaborations are essential. Together with the laboratory for solid state NMR, our lab forms the department of physical chemistry, itself a member of the Nijmegen Science Research Institute of Matter (NSRIM) research school. The research school also includes the high-magnetic field laboratory, as well as the laboratory of bioorganic chemistry, which focuses on the biological mimicking of nanotechnologies.

Moreover, our research is closely affiliated with the Nijmegen Center for Molecular and Life Sciences and the Center for Molecular and Bioinformatics. The combination of a high-magnetic field lab with high-field NMR creates an extremely strong center for NMR research, and in fact, NSRIM is one of the few institutes worldwide for high-magnetic field studies. Others are at Grenoble in France, in Florida in the United States, and in Japan.

All together this creates a unique research environment in which the critical mass is present to further develop high-field NMR methods in a strong biological research setting. The Netherlands has a strong position worldwide in biophysical chemistry, with not only a number of leading NMR groups, but also other excellent biophysical chemistry groups working in areas such as molecular dynamics, biospectroscopy, and x-ray crystallography.

Some other important structural, functional biology ?hotspots? in Europe include the European Molecular Biology Laboratory, the EBC (Hingston, UK), the Max Planck Institutes, ETH in Zurich, Biozentrum in Bazel, Berlin, MRC Oxford and Cambridge, the European NMR facilities, and the x-ray labs in Strassbourg, Lund, and Uppsala.

Qualifications, Skills, and Training

The most important qualification for a successful scientist is a passion for science, and as a biophysical chemist you have to be resourceful and able to bring together skills and ideas from a broad range of disciplines. To find a position in this expanding field, either in academia or in the biotechnological or pharmaceutical industry, a PhD is required and often some training at the postdoctoral level. The best training is to spend some time at one of the aforementioned centers in Europe or the United States.

Can you switch fields? As a general rule it is easiest to turn to biophysical chemistry for those that have a physics or (bio)chemistry background. For a biologist to be effective requires some additional training in physics and mathematics. Nevertheless, whatever your primary discipline, the world is your oyster in this fascinating and expanding field that connects life and natural sciences.

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