The first decoded moss genome: From all-conquering country dweller to producer of medicines
Mosses are of enormous interest for science, as they represent a crucial stage in evolutionary history: They are thought to be representative of the first plants to make the transition from water to land, 450 million years ago. To survive, they had to adapt to extreme temperature fluctuations, drought and high UV radiation. Now, moss research has succeeded in a major coup: As a consortium of 70 scientists led by researchers in Freiburg recently reported in the specialised Science magazine (2007,13 Dec, online), the Physcomitrella patens moss genome has now been fully decoded - the first model genome for a plant whose evolutionary development is somewhere between algae and flowering plants. The findings are relevant not only for science but also for business. How mosses cope with stressful climactic conditions is also of practical application for modern crop breeding. Moreover, a biotech companies founded eight years ago in Germany by Freiburg University hopes to use this sequenced moss as a producer of medicines.
To date, there exist only a few fully decoded genomes from multicellular organisms. Aside from the human, the mouse and the nematode Caenorhabditis elegans, a number of plants have also made it onto the list of sequenced organisms. Given the still high cost of sequencing, only a small number of plants have complete genome sequences. Up to now, flowering plants such as thale cress (Arabidopsis thaliana) or poplar have been of central interest, as well as some algae, and crops such as rice or barley, which have only recently begun the process of genome decoding under German coordination. (More…) Whereas algae began life at the very beginning of plant development, flowering plants find themselves at the opposite end of evolutionary history. To date, however, a representative has been lacking among the model genomes for the crucial evolutionary step of plants’ transition from water to land and the development of multi-cellular life, approximately 450 million years ago. This gap has now been closed by a scientific consortium of 70 different teams, who submitted their decoding of the Physcomitrella patens genome to Science magazine (2007, 13 December, online).
Seven German research groups contributed to this mammoth task, alongside academic institutions from the United States and Japan. The group of scientists headed by Stefan Rensing at the University of Freiburg, which itself is part of the team led by moss research pioneer Ralf Reski at the Institute for Plant Biotechnology, had a particularly important role to play in the project. For over twenty years already, the Physcomitrella patens moss has been Reski’s first choice as object of study. "When I began researching Physcomitrella it was purely a niche area of research. I would never have dared to hope that one day I would decode the entire genome of the moss", says Professor Reski today.
Mosses: More complex than algae, although less so than flowering plants
Mosses have a much more complicated structure than algae, but unlike flowering plants they do not have sophisticated vascular bundle systems or intricately-shaped reproductive organs. The transition from water to land was a major step for plants and is related to changes in many cellular processes. In order to survive, the newly land-dwelling plants needed to adapt to extreme temperature fluctuations, drought and high UV radiation, the likes of which did not exist in water. All of these altered requirements are now reflected in the moss genes, as the scientists were able to determine following first comparisons with other genomes.
Alongside, the moss had a number of pleasant surprises in store, for example clues as to how tolerances to drying-out or plant hormones’ modes of action have developed. Anyone who has ever left an indoor plant to dry out has given a practical demonstration of how this tolerance to drought, although an important feature, is no longer carried by most flowering plants. The sequence from the small Physcomitrella patens moss shows that the original land-dwelling plants were likely to be tolerant of dry conditions and that this property has only been lost in more modern plants. The moss genome also shows that - already among the first land plants - plant hormones steered various crucial stages in development and growth. For algae, however, such hormones were yet to appear.
The researchers at the Cologne Max Planck Institute, who were also involved in the sequencing project, were primarily interested in how DNA damage in Physcomitrella is repaired. This process is significant in humans in the defence against harmful environmental influences, and is also involved in the development of cancer and aging. "DNA damage in Physcomitrella is repaired very precisely, which is undeniably a result of the high stability of the Physcomitrella genome," says Bernd Reiss, a group leader at the Max Planck Institute in Cologne, of the research results. "From human medical research, we know that errors in the genome can lead to disease. In this respect, it is of great interest to get a clearer picture of the mechanisms that contribute to this genomic stability."
Businesses are also taking an interest in mosses
The moss is now gaining attention from a number of quarters, in particular because it is easy to genetically modify and can be cultivated in a small space. BASF was the first company to recognise the great potential of this research and from 1999 has invested a two-digit million figure in the work being carried out by Ralf Reski and his team at the University of Freiburg. "This cooperation probably provided the impetus for the various national funding organisations in the United States, England and in particular Japan to fund large-scale moss research," says Reski in retrospect.
In 1999, together with his colleague Gunther Neuhaus, Reski spun off the company greenovation Biotech, which is based on the development of a moss-based photo-bioreactor. In the future, this company will manufacture protein-based drugs, and will be in competition with current approaches, which function based on microorganisms or animal cells. The use of bacteria has its limits, as they cannot perform specific biochemical reactions – for example, they are not able to bind sugar building blocks to protein molecules. This process of glycosylation is reserved to eukaryotic cells, which have an endoplasmic reticulum (ER) and Golgi apparatus at their disposal. Because the protein sugar code is playing an increasingly important role in therapeutic approaches, glycosylation in drug production has also become an area of interest, the aim being to develop proteins with a ‘human' natural sugar structure, which would lead to the development of more effective drugs. Many research groups are working to optimise this ‘sugar coating’ in mammalian cells, and it has now been recognised that a plant-based system, as provided by mosses, can also aid in targeted glycosylation development.
Greenovation Biotech has now occupied this niche and has begun around a dozen cooperations, both with biotechnology companies as well as with pharmaceutical companies. The goal is to become established as a production system early in the drug development stages. Greenovation is intending to carry out production up to a clinical phase II, with the third phase of clinical testing being undertaken in cooperation with other production partners.
Good news for mosses as drug producers
Replacing established production systems in the pharmaceutical industry is not an easy business - greenovation Biotech were first able to report good news as recently as October: Sartorius Stedium biotech from Göttingen, a Germany-based provider to industry of process and laboratory technologies in biopharmaceutical production will be participating in the construction of the first photo-bioreactor on an industrial scale in Heilbronn. The plant will be operational 2010. It was financed by a round of financing totalling 5.4 million euros that was closed in 2006, and in which the Zukunftsfonds Heilbronn (Future Fund Heilbronn) played a vital role, providing 3.5 million euros.
The optimisation of production technologies is also continuing in one of the projects between the company and the universities of Freiburg and Karlsruhe supported by the BiochancePlus program from the German Federal Ministry of Education and Research (BMBF). "With the deciphered moss genome, we now have the blueprint to make plant biotechnology even safer and more efficient, which will be to everyone’s benefit," says Reski. And Rensing adds: "The decrypted moss genome is a fundamental prerequisite for modelling the life processes of this simply constructed plant." This area of research is also supported by the BMBF in the framework of the Freiburg Initiative for Systems Biology (FRISYS).