Florian Schmidt is the 2022 Grand Prize Winner for his work developing Record-seq, a breakthrough technology that noninvasively records the activities of gut microbiota and advances the understanding of gastrointestinal health Science & SciLifeLab Prize for young scientists.
Schmidt’s essay describes engineer cells from Escherichia coli (E. coli ), a bacterium commonly found in the human gut to act as sentinels, migrating through the gastrointestinal tract, recording in their DNA the transcriptional response to various interactions between them and the host. Unlike RNA, which is relatively short-lived and fragile, the E. coli Sentinel cells record information at different time points that can be efficiently and noninvasively retrieved from host feces by deep sequencing.
“Schmidt’s work is highly creative and a technical milestone. His research follows a path from concept to realization and has led to the development of a unique method that allows bacterial sensory cells to detect changes in their host’s gut. Tracking the response to interactions between different microbiota and the host could greatly improve our understanding of how the microbiome influences health and disease,” said Sacha Vignieri, associate editor at Science.
Intrigued by the idea of repurposing the adaptive microbial immune system CRISPR, Schmidt and his colleagues used the CRISPR spacer acquisition complex to engineer Record-seq and adapted it to store and record transcription responses as DNA to learn about conditions in the gut to report.
Creating the best method
As a new technology, Record-seq was not originally intended as a noninvasive tool to study the gut microbiome, Schmidt said. However, when its full potential for recording the cell history of bacteria was discovered, he and his colleagues Tanmay Tanna and Jakob Zimmermann from the labs of Randall Platt at ETH Zurich and Andrew Macpherson at University Hospital Bern worked on using Record-seq im gut microbiome to begin with.
Current methods of examining the intestinal tract include invasive surgery to measure intestinal activity or stool and blood-based tests that do not provide information about specific conditions in the intestine. Record-seq-derived E. coli Cells insert a lens into proximal sections of the intestine and allow the adaptations and behavior of the microbiota to be examined non-invasively.
“Other scientists have previously developed biosensors that can detect the presence of a specific small molecule…but they are fine-tuned to detect the presence or absence of a small group of molecules, but blind to everything else,” explained Schmidt. “With Record-seq, we’re removing that proverbial blindfold… anything the bacteria interacts with and changes their behavior could be captured.”
Hopefully, researchers can now use Record-seq as a tool to discover new biomarkers relevant to nutrition and disease, Schmidt said. This could enable further translational efforts in diagnostics and therapy in the future.
The future of gut health
Schmidt and his colleagues fed mice with it E. coli cells to test the recording of transcriptional information in the gut. The group was able to glean this information by DNA sequencing cells from the mice’s feces, prompting the researchers to change the mice’s diet to test the intricacies of the records.
Record-seq was able to capture significant customizations of E. coli adapt to different diets and retain this information. While both RNA sequencing (RNA-seq) and Record-seq could distinguish between a standard chow or starch diet, only Record-seq retained information from a previous diet after a switch. Record-seq also stores information about the length of the gastrointestinal tract, while much information is lost from fecal RNA-seq samples.
These insights into the hidden life of microbiota in the gut are intriguingly complex, and Record-seq opens a new window to understanding how diet, inflammation, and microbial interactions in the gastrointestinal tract affect health and disease.
“Think of all the diseases and interactions that affect your gut, and also consider that we could use this to study how people interact with their diet. The variety of ways different people respond to different diets is amazing and can also contribute to pathological conditions such as malnutrition or obesity. Record-seq could be used to investigate and inform treatment decisions for these diseases and food intolerances,” said Schmidt.
That Science & SciLifeLab Prize for Young Scientists recognizes that global economic health depends on a vibrant research community that must inspire the best and brightest to continue in their chosen research areas as they begin their scientific careers. The grand prize winner will receive a prize of $30,000.
“What is striking about the winners of the Science & SciLifeLab Prize is her ability to clearly explain her exciting scientific discoveries and place them in the broader context of biology, medicine and even pressing societal challenges. Such is the case again this year, with three essays describing different types of microbial research and one on the regulation of a protein involved in cell growth in health and disease,” said SciLifeLab Director Olli Kallioniemi. “We at SciLifeLab look forward to participating in this award and hope this recognition will advance the careers of these next-generation research leaders and popularize their research. Congratulations to all four winners of this year’s awards.”
Stefany Moreno-Gámez is a winner for her paper “How Bacteria Navigate Different Environments”. Moreno-Gámez received a bachelor’s degree from Universidad de los Andes and a Ph.D. from the University of Groningen and ETH Zurich. She is currently a postdoctoral fellow at the Massachusetts Institute of Technology. Her research focuses on how dietary and host glycans influence ecological and evolutionary dynamics in the gut microbiome.
James L Daly is a winner for his paper “Endosomes, Receptors and Viruses”. Daly received Bachelors and Ph.D. Degrees from the University of Bristol. After completing his studies, he was awarded a Wellcome Early Career Award bursary and moved to the Department of Infectious Diseases at King’s College London. His current research continues to explore the molecular interface between neuropilin receptors and viruses and the potential for antiviral inhibition of this process.
Daniel Simoneschi is a winner for his paper “Uncovering the degrader of D-type cyclins”.
Simoneschi received a bachelor’s degree from Manhattanville College and an MPhil and Ph.D. Degrees from the Vilcek Institute of New York University. He is an Assistant Professor in the Department of Biochemistry and Molecular Pharmacology at NYU, where he studies molecular and cellular mechanisms by which Cullin RING ubiquitin ligases regulate cell cycle execution.