On the road to high-throughput biology

Establishment of new DNA Biofoundry "MaxGENESYS" at MPIterMic

August 31, 2020

Daniel Schindler, head of the new Biofoundry MaxGenesys at the MPIterMic, explains what the MPG-wide research service will offer in the future, and how scientists “scramble” synthetic chromosomes.

Daniel, you are the research director of the new and MPG-wide Biofoundry MaxGENESYS. What is a Biofoundry?

Well, Biofoundries have become very fashionable in recent years. Basically, it's about cloning or synthesis of large DNA fragments or pathways on robotic platforms in large scale. It enables high throughput in small volumes.

What are the advantages of such a platform?

It makes work more efficient, and you achieve things that humans could never do themselves. For example, with manual pipetting of this magnitude, errors happen; the machine is programmed, thus transfers are accurate. MaxGENESYS is primarily focused on assembling DNA into complex units and of course analysing and verifying them. But It is worth noting that the platform will be able to do considerably more.

What are your own experiences with Biofoundries so far?

I worked on such machines in Edinburgh and Manchester after my PhD, but I only used single elements of these foundries. In my opinion, "standalone" machines are preferable, i.e. individual elements that can be operated by several researchers in parallel, as opposed to a complete system where everything is closely linked. This does not exclude a later completely integrated system, but in the academic field you usually need flexibility.

What will MaxGENESYS offer in the future?

The MaxGENESYS machines can be used quite variably. They will carry out nucleic acid extractions, pipette chemical reactions, create next generation sequencing libraries and perform chemical screenings. The system is complemented by an acoustic dispenser, which enables reactions in the nanolitre range and therefore brings enormous cost savings. There will be a robot that automatically selects, picks and transfers colonies into a specific culture medium; then a robot that can transfer these colonies in high throughput into other formats, or into solid or liquid media for characterization or high throughput genetic crossings. It will also provide a data documentation system.

The advantage of such a flexible platform is that projects can be handled individually.  In case of a request, even large strain libraries can be copied and characterized without any problems. MaxGENESYS will not only be available to Marburg Research, but to all Max Planck Institutes.

How difficult is it to handle such a platform?

Well, the big liquid handling robot is a bit more demanding, but many other machines are not at all. A master student can learn to operate it independently within an hour. The Liquid Handling Robot protocols have to be trained and optimized, but once they are established, they will become part of the laboratory routine.

What is the main part of your work in MaxGENESYS?

It starts with consulting during the planning of experiments. It is also about communicating what can and cannot be realised. For special requirements the robot has to be optimized, for example that it pipettes certain solutions without errors. It is also a question of whether the project is so extensive that it is worth working with a liquid handling robot. But there are also devices where everything is already specified, the software is set and the machines are ready-to-go.

The large devices that will be used in the Biofoundry MaxGENESYS are still in the acquisition phase. However, during our conversation Daniel Schindler was already able to literally pull this little device out of his coat pocket: A nanopore sequencer not bigger than a candy bar. It can even be used to sequence the entire human genome.

In addition to MaxGENESYS, you will lead your own research group under the roof of Tobias Erbs' Department of Biochemistry and Synthetic Metabolism. How did your come to the field of Synthetic Biology?

I did my doctorate here in Marburg under Torsten Waldminghaus supervision. There I started building synthetic chromosomes in bacteria. Afterwards I went on to Edinburgh to Patrick Cai. He is the coordinator of the synthetic yeast project which aims to synthetically reconstruct the 16 chromosomes of yeast piece by piece, including the integration of exciting functions into the newly designed genome. For example SCRaMbLE, which is short for Synthetic Chromosome Recombination and Modification by LoxP-mediated Evolution. This technique enables to generate a gigantic pool of random genomic variants from a single yeast cell.

In other words, synthetic biologists not only construct, they also "roll dices"?

Exactly. If I confront the genomic variants with certain stress situations, I can select for individuals with improved abilites. For example, by increasing the ethanol content in the medium I can identify isolates that tolerates more ethanol. Or by incubating at higher temperatures, heat resistant strains can be generated. This is rather application-oriented research, which is also of interest for industrial biotechnology.

When will MaxGENESYS start?

I have been in Marburg since August, and the first team members will start in September. MaxGenesys will need some time to reach full capacity, as large-scale equipment is still in the procurement phase and then will have to be built up, and put into operation - which is not easy under the current conditions. Some companies are dependent on suppliers and the pandemic is causing delays. I hope, however, that all the equipment will soon be on site. The first proof-of-concept experiments will start in the upcoming weeks.

What synergies do you see for your research here in Marburg?

In Marburg there is actually a lot of overlap: Mr. Mösch, who is a yeast expert, Gerd Bange in functional and structural biochemistry, Anke Becker with enormous experience in laboratory automation. The advantage is that I already know many researchers here, it is relatively easy to start up again. But also the other new research group leaders offer enormous potential for synergies: Henrike Niederholtmeyer with her approaches in cell-free biology, Georg Hochberg with his research on evolutionary chemistry and, of course, Tobias Erb with his synthetic metabolic pathways.

What are your current tasks?

Currently I am preparing projects and setting up the laboratory, expanding the team and initiating collaborations. It is important to support young, motivated people - so applications for theses at all levels are always welcome!

Daniel, thank you very much for the interview, and all the best for your start at the MPIterMic!

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