Christoph Thaiss has been named the 2018 Grand Prize winner of the Science & SciLifeLab Prize for Young Scientists for work that implicates the microbiome — the community of bacteria that live within organisms like plants and animals — as a common culprit underlying hallmarks associated with human obesity, a complex and multifaceted disease.
Thaiss and his team discovered that specific molecules produced by intestinal bacteria are altered in three specific factors that have each been associated with human obesity: the disruption of the biological clock, recurrent weight gain and enhanced susceptibility to infection.
"A deeper understanding of the factors controlling the activity of the microbiome will enable us to understand the specific mechanisms underlying environmental impacts on human disease, and may provide us with actionable predictions of how certain lifestyle changes can have preventive or therapeutic effects," said Thaiss.
The molecular processes involved in metabolic disease are poorly understood, in part because both genetic and environmental factors contribute to its onset. "The metabolic effects of obesity are also largely variable in different individuals and influence multiple different organ systems, and as such, the study of obesity and the development of new therapeutic strategies require integration of technologies from many different scientific disciplines," said Thaiss.
The prize, now in its sixth year, recognizes promising early-career scientists who conduct groundbreaking life-science research and includes a grand-prize award of $30,000. It is supported by SciLifeLab (Science for Life Laboratory), a national center for advanced molecular life sciences in Sweden and the journal Science. The prize is also made possible through the kind support of the Knut and Alice Wallenberg Foundation, which promotes scientific research, teaching and education. It is also the largest private financier of research in Sweden.
"Understanding the interplay between diseases like obesity and the bacteria that live in our gut may suggest new approaches for therapeutic intervention," said Valda Vinson, deputy editor of Science.
"The human lifestyle has dramatically changed over the last century, and so has our susceptibility to various metabolic diseases," said Thaiss, an assistant professor at the University of Pennsylvania. In his grand-prize winning essay, " Microbiome dynamics in obesity," which will appear in the November 23 issue of Science, Thaiss' findings suggest that elements of the modern human lifestyle like the disruption of the biological or circadian clock by shift work or erratic weight management by cycles of diets may impact metabolic health through their effects on the intestinal microbiome.
Previous research has linked circadian clock disturbances to obesity and high blood sugar, and Thaiss discovered that the gut microbiome in both mice and humans undergoes fluctuations in a 24-hour rhythm. He then showed that such daily oscillations in the intestinal microbial community influence the circadian biology of the host. Interestingly, Thaiss observed that disruption of host circadian rhythms by phenomena like jet lag altered the intestinal microbiome. These alterations predisposed the rodents and humans to obesity and glucose intolerance.
Thaiss also studied microbiome disruption on longer time scales, as the rapid weight regain of formerly obese individuals after successful weight loss — a phenomenon commonly known as the "yo-yo effect" — continues to puzzle scientists. In mice, Thaiss found that a period of obesity induced long-lasting alterations in microbiome composition that persisted even after the host organism returned to normal weight — "memory-like" behavior that predisposed formerly obese animals to accelerated weight regain.
Thaiss also addressed the enhanced susceptibility of obese and diabetic individuals to intestinal infection and systemic inflammation. Intestinal epithelial cells, which line the intestinal tract, normally provide a tight barrier that separates intestinal bacteria from the circulatory system. His analysis of obese and diabetic mice revealed that breakdowns in the intestinal epithelial barrier led to the transport of bacterial molecules to the bloodstream, which caused inflammation. Importantly, Thaiss confirmed these results in human patients, where chronic high blood sugar strongly correlated with the levels of microbial products detected in the circulation.
"Since most of our work was carried out using mice to model obesity and its metabolic complications, the most important next step will be to translate our findings to human obesity. Our first insights indicate that the fundamental mechanisms we discovered can be applied to human biology. Whether our approach can be used to improve metabolic health in humans is an exciting question that we are actively pursuing," said Thaiss.
Thaiss will receive the award for his research in the field of Translational Medicine in Stockholm, Sweden, on December 13, during an award ceremony and dinner at the Grand Hôtel in the Hall of Mirrors, which originally hosted the Nobel Prize ceremony from 1901 to 1929. His work will also be featured at a symposium on December 12 at Karolinska Institutet in Stockholm, Sweden.
"Congratulations to all the winners of the 2018 Science & SciLifeLab Prize for Young Scientists. I am very impressed by the quality of all four winning essays, as well as the ground-breaking research that these young scientists have performed. We very much look forward to welcoming the winners to Stockholm and Uppsala in December for the prize ceremonies," said SciLifeLab Director Olli Kallioniemi. "We have had the pleasure of collaborating with Science for six years now to award this prize. Based on the remarkable track record of the previous winners of this prize, I am sure that these 2018 winners are also likely to become future leaders in their fields."
The Science & SciLifeLab Prize for Young Scientists is an annual prize aimed at rewarding young scientists at an early stage of their careers. The categories for the award are Cell and Molecular Biology, Ecology and Environment, Genomics and Proteomics, and Translational Medicine.
Applicants for the 2018 Science & SciLifeLab Prize for Young Scientists submitted a 1,000-word essay that was judged by an independent editorial team organized by the journal Science. Its content was evaluated on the quality of research and the applicants' ability to articulate how their work would contribute to the scientific field.
The 2018 award also recognizes three category winners, whose essays will be published online in the journal Science. A podcast featuring additional commentary from Thaiss and the other winners will be available on November 23.
The 2018 category winners are:
Tim Wang: For his essay on the topic of genomics and proteomics, "Paring down to the essentials ." Wang received his undergraduate degree from the University of California, Berkeley and his doctoral degree from the Massachusetts Institute of Technology. Wang is currently investigating the structural and functional organization of neocortical circuits as a postdoctoral fellow at the Janelia Research Center in the laboratory of Karel Svoboda.
Matthew Savoca: For his essay on the topic of ecology and environment, "The ecology of an olfactory trap ." Savoca received his undergraduate degree from Cornell University and his Ph.D. in ecology from the University of California, Davis. Savoca is currently a postdoctoral researcher at the Hopkins Marine Station of Stanford University studying the foraging behavior of baleen whales and their possible interactions with plastic debris.
Ruixue Wan: For her essay on the topic of cell molecular biology, "A key component of gene expression, revealed ." Wan received her undergraduate degree from Sun Yat-sen University and her Ph.D. from Tsinghua University. Wan is currently a postdoctoral fellow at Tsinghua where she is conducting research on structural and biochemical investigations of the spliceosome, a complex molecular machine that functions inside of cells, to elucidate the mechanism of pre-mRNA splicing and the regulation of the spliceosome.