Florian Schmidt, Grand Prize Winner of the Science & SciLifeLab Prize for Young Scientists, has always been fascinated by science – but ending up in molecular biology was no sure thing.

The one thing that got Florian Schmidt fascinated beyond constructing with Lego bricks was always some form of science. The myriad of sports and hobbies he tried throughout his youth did not measure up to the exploration of the unknown. What form of science he would take on was far from a certain thing, however. He was fascinated by everything from space travel to ancient Egypt and archaeology. But throughout high school, there was something about molecular biology that drew Florian in – so much so that he enrolled in the Molecular Biotechnology program at Heidelberg University.

I think this was the point where I truly realized I wanted a life in research and science

At university, Florian heard about the International Genetically Engineered Machine (iGEM) competition, a worldwide competition awarding interdisciplinary teams that design and build exceptional synthetic biology projects. He was immediately hooked.

“Taking an engineer’s approach to molecular biology and constructing cellular machines from molecular building blocks felt like a revival of using Lego bricks for adults” says Florian Schmidt.

In this competition, Florian and his team developed a tool, called NRPS Designer, which predicted the optimal modular composition of synthetic non-ribosomal peptide synthetases (NRPS) for the production of any desired peptide. For this project, the team was awarded first place in the 2013 iGEM competition.

This project gave Florian a glimpse into what a research career would be like, and he got to experience the feeling of persevering through failures and finally reaping the fruits of that work – the joy of creating solutions to previously unsolved problems.

“I think this was the point where I truly realized I wanted a life in research and science” says Florian Schmidt.

Exploring the vastness of the gut
The human gut contains a plethora of bacterial and human cells that interact with one another and the foods that we eat. Learning more about these interactions is important for a better understanding of health and disease related to the gut. We need to know how the molecular environment responds to different foods, antibiotics, inflammation, or pre- and probiotics. 

The problem with many types of research is that the gut either needs to be cleaned out or cut open to get a good view or retrieve a sample. This, of course, disturbs the inhabitants and makes them change their behavior, resulting in an incomplete picture of how they would act without interruption – not to mention the methods being quite intrusive to the subject or patient.

To study the molecular environment of the gut in a non-invasive way, Florian Schmidt made use of gene expression. Every cell carries its own genome encoding information in the form of DNA. The cell transcribes selected parts of its DNA – individual genes – from the permanent storage form of DNA into RNA molecules. Next, the cell can use these RNAs to translate each one of them into a specific protein with a certain function. Therefore, measuring the RNA molecules inside a cell is a reliable method to get an idea about the behavior and the environment of the cell. These behaviors cannot be directly measured, but they can be inferred based on the gene expression of the cell.

My vision and hope are that we can eventually bring these cells into humans, preferably in the form of a tasty yogurt

RNA is short-lived in order for the cell to constantly adapt to changes in its environment by expressing the right genes. Therefore, methods that have been developed by researchers to measure the RNA molecules inside the cell struggle to give us a full picture of what is happening.

To get around this, Florian and colleagues constructed and developed a tool that could be described as a space probe, that enters and travels through the gut and responds to the environment, recording the surrounding RNA molecules.

They used the bacterium Escherichia coli, which not only can survive in the mammalian intestine, but also has the ability to react and adjust its own gene expression in response to the environment that it encounters. These cells were engineered to keep a record of the RNA molecules that they are transcribing – the cells can essentially record their own transcription.

These space probe cells can then be fed to mice, and hopefully to humans in a not too distant future. The probes enter the gut, travel through the entire intestine, sense and experience their environment and change their own gene expression in response. The probes can also interact with other microbiota inside the gut, ask them questions and learn from them about the environment. 

At the end of their journey, the probes exit the intestine almost unnoticed via the feces. The researchers can retrieve them noninvasively, without disrupting the intestine, and in a manner that is risk free and painless for the mouse or human who ingested them. The DNA is then extracted, which allows Florian to get a glimpse of what is going on inside the intestine. This can help us to better understand how the bacteria reacts to different diets and whether the gut of this particular person is healthy or diseased. All of this has already been achieved by Florian, but he is not stopping there.

“My vision and hope are that we can eventually bring these cells into humans, preferably in the form of a tasty yogurt that anyone would be happy to eat so that the cells traverse the gut of a human instead of the gut of a mouse. Then doctors could use the information recorded by our sentinel cells as an additional tool to examine the intestine, understand the individual nutritional needs of their patients, allowing them to live a longer and healthier life as well as guide treatment decisions – all without having to go through risky and painful surgeries or a colonoscopy” says Florian Schmidt.

Read Florian Schmidt’s essay in Science.