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Biomolecular Sciences: driving industrial biotechnology

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02/02/2014

Biomolecular Sciences: driving industrial biotechnology 

Microorganisms are bustling with chemistry. In fact, they are the richest and most diverse reservoirs of chemical activities on our planet. Their activity is essential to sustain the elemental cycles of carbon, nitrogen, phosphorus, and sulphur.

The field of biotechnology, exploiting these microbial activities for industrial purposes, is currently thriving due to advances in genetic control of microorganisms and fermentation technologies. Experts even postulate that biotechnology will provide sustainable solutions for a number of the grand societal challenges. Further, while pathogenic microorganisms are increasingly threatening our well-being, each of us could not exist without a huge number of commensal microorganisms residing in our guts. Thus, having control over microor- ganisms is of eminent importance for human health.

FUNDAMENTAL SCIENCE, A PREREQUISITE

While many possibilities await us in the microbial reservoir, we are still far from truly designing, engineering, and constructing novel enzymes and ultimately robust (synthetic) cells. Key to harvesting the amazing potential of microorganisms and to gain their full control is fundamental research. Furthermore, as a guarantor for innovations, only fundamental research will allow uncovering the unknown and the unexpected.

Dutch microbiology can proudly look back to an impressive more than 100-year history of excellent microbial research, spearheaded by pioneers such as Van Leeuwenhoek (already in the 17th Century and the first person to ever see microbes), Beijerinck, Kluyver and others, which has led to major breakthroughs with significant commercial value. Next to building solid foundations in science, applied research is very important, in which particular ground-breaking fundamental insights are succesfully translated into industrial applications.

TRANSLATING SCIENCE INTO INNOVATIVE APPLICATIONS

The Groningen Biomolecular Sciences and Biotechnology Institute (GBB) is a multidisciplinary research institute with an extremely strong fundamental pillar, but also uses its unique expertise to address challenges in applied research. The institute has many industrial collaborations that have directed various innovative biotechnological applications of enzymes and micro- organisms. The 12 research groups of the institute – having firm roots in chemistry, biophysics, and biology – are grouped in the two focal areas:

Molecular mechanisms of bioprocesses and Physiology and systems biology, capturing the whole spectrum from molecule to cell. Specific expertise areas are gene regulation, protein engineering, membrane biology, cell biology, and systems and synthetic biology. GBB has state-of-the-art in house facilities for single cell- and single molecule analyses, high-resolution optical and electron microscopy, modern omics technologies and advanced cell engineering. Exemplary showcases of GBB’s fundamental and applied research are best demonstrated by the following four examples: 

Protein Transport System

Bacteria are ideal vehicles to produce proteins of interest. They can be grown at a large scale using cheap nutrients and, importantly, they have the ability to secrete proteins into the extracellular medium to facilitate recovery and to obtain high protein yields.

The bacterial secretion system (denoted as the Sec- system) in its minimal form consists of an energy-driven motor protein that pushes unfolded proteins through a narrow pore in the membrane whereupon these proteins fold on the outside of the cell. GBB studies the mechanism and structure of the Sec-system in detail through integrative multidisciplinary approaches combining advanced reconstitution methods with bio- chemical characterization and single molecule analysis.

Singel Cell Analysis

This example of top-notch fundamental research, involves strong and productive collaborations among research groups within GBB complemented by the neighbouring partner institutes, focusing on synthetic organic chemistry and materials science. It also con- tributes to major research activities on other microbial transporters, from basic insight into their translocation mechanisms to innovations in membrane engineering, altogether offering unprecedented solutions for current challenges in industrial biotechnology.

For decades, biologists thought that individual cells of a microbial population are identical. With the advent of novel microscopic techniques, researchers from GBB and colleagues elsewhere have recognized that in fact, such populations can be quite heteroge- neous, because of an inherent randomness in certain biological processes. Such heterogeneity has significant consequences. For instance, so-called persister cells are no longer sensitive to antibiotics and can give rise to re-occurring infections. Alterna- tively, if differently productive populations are present in biotechnological fermentation processes, this could have enormous consequences for production yields.

Researchers from GBB contribute by developing and implementing new analytical techniques (microscopy or single cell metabolomics) to investigate the intriguing molecular mechanisms that lead to such phenotypic heterogeneity. This research line is an excellent example of fundamental research with huge potential for application spin offs. Notably, without this research, we would still think that isogenic cells in a microbial population are identical and, thus, we would miss chances for new and improved cellular productivity and therapeutics.

Biocatalysis

Enzymes fulfil essential roles in the cell and are at the heart of each metabolic activity. Due to their tremendous rate of catalysis and exquisite chemical selectivity, enzymes are highly attractive as biocatalysts in biotechnological applications. Industrial processes often involve non-biological conditions and an advanced level of enzyme discovery and/or engineering is generally required for successful application.

Through an integrative effort of enzyme discovery and enzyme engineering extended with computational and experimental studies of their structure-function relationships, GBB develops enzymes that are highly relevant for biorefinery processes, production of platform chemicals, healthy food additives, and added-value products such as antibiotics. For instance, novel penicillin acylases have been discovered and developed at GBB that now form the basis of actual industrial processes for the manufacturing of semi- synthetic antibiotics. Glucanotransferases (GTFs) acting on starch have been engineered and are currently used for the synthesis of modified starches that are marketed for various food applications. Oxidative biocatalysts have been created specifically for the synthesis of biomass-based polymer building blocks and pharmaceuticals. 

Synthetic Cell

The bottom-up assembly of a living cell from basic molecular components is emerging as a new and exceptionally exciting frontier in science and engineering. Despite increased chemical and physical understanding of biomolecules and their mutual interactions, it remains elusive how they together form a cell that can autonomously grow and replicate.

GBB and its partners collaborate in large-scale programmes to create a functioning synthetic cell from biomolecular building blocks. Such bottom-up synthesis of a cell is not only a formidable engineering challenge, but will also allow to unravel the principles of biological processes in a truly fundamental way. Such a detailed understanding will simultaneously bring unprecedented opportunities for innovative applications in health, biotechnology, and materials.

GBB foresees important spin-off results in the form of advanced drug delivery systems, drug-screening methods, and bionanodevices for multiplex detection of molecules. 

GBB hosts an international team of almost 200 scientists who operate at the forefront of their research fields and additionally educate the next generations of scientists. Towards this end, GBB is formally accredited as a Research School by the Royal Netherlands Academy of Arts and Sciences. Due to its training expertise, GBB is an acknowledged partner in Master and Doctoral training networks. The institute accommodates many exchange students, amongst others being sup- ported via Erasmus Mundus, South-American, and Asian Scholarship programmes. It also coordinates and participates in a large a number of Marie Curie Initial Training Networks of the European Union.

The high level of training is best exemplified by the successes of students at GBB. For example, students from Groningen were crowned World Champions in the International Genetically Engineered Machine (iGEM) student competition of 2012. Moreover, the students are very successful on the academic and industrial job market and have an excellent success rate of obtaining their own research grants.

The bottom-up assembly of a living cell from basic molecular components is emerging as a new and exceptionally exciting frontier in science and engineering. Despite increased chemical and physical understanding of biomolecules and their mutual interactions, it remains elusive how they together form a cell that can autonomously grow and replicate.

GBB and its partners collaborate in large-scale programmes to create a functioning synthetic cell from biomolecular building blocks. Such bottom-up synthesis of a cell is not only a formidable engineering challenge, but will also allow to unravel the principles of biological processes in a truly fundamental way. Such a detailed understanding will simultaneously bring unprecedented opportunities for innovative applications in health, biotechnology, and materials.

GBB foresees important spin-off results in the form of advanced drug delivery systems, drug-screening methods, and bionanodevices for multiplex detection of molecules.

HUMAN POTENTIAL AND TRAINING

GBB hosts an international team of almost 200 scientists who operate at the forefront of their research fields and additionally educate the next generations of scientists. Towards this end, GBB is formally accredited as a Research School by the Royal Netherlands Academy of Arts and Sciences. Due to its training expertise, GBB is an acknowledged partner in Master and Doctoral training networks. The institute accommodates many exchange students, amongst others being sup- ported via Erasmus Mundus, South-American, and Asian Scholarship programmes. It also coordinates and participates in a large a number of Marie Curie Initial Training Networks of the European Union.

The high level of training is best exemplified by the successes of students at GBB. For example, students from Groningen were crowned World Champions in the International Genetically Engineered Machine (iGEM) student competition of 2012. Moreover, the students are very successful on the academic and industrial job market and have an excellent success rate of obtaining their own research grants. 

PARTNERING IN SCIENCE

With its vast expertise and modern facilities GBB is an excellent partner for first-rate biomolecular and cellular science as well as for challenging demand- driven biotechnological research. Furthermore, because of its strong track record and experience in (inter)national public-private-partnerships (PPP) that are supported by various companies, GBB is well aligned to the Horizon2020 programme of the European Union. Here, GBB aims to contribute to the three defined pillars: Excellent Science, Industrial Leadership, and Societal Challenges. Of particular interest are programmes that will be funded via the European Research Council and different PPP-instruments, for instance those within Future and Emerging Technologies (FET) and Leadership in Industrial Technologies (LEIT). 

References

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