From England to Germany via France and the US: Microbiologist Ruth Ley has not only worked on a diverse array of bacteria over the course of her career, she has also encountered a cultural difference or two between various countries.
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Exploring the Microbial Cosmos
The human body is home to countless microbes. The intestinal tract, in particular, is colonized by innumerable bacteria. As a young environmental microbiologist, Ruth Ley never imagined that she would one day find herself interested in the human gut and the microbiota that reside in it. Today she conducts research at the Max Planck Institute for Developmental Biology in Tübingen, investigating the role the countless intestinal bacteria play in our health.
TEXT CORNELIA STOLZE
he different stages of her ca- for instance, on these tours of the her PhD at the University of Colorado, reer read like a travel agen- Rocky Mountains. I’m an awful skier,” she often had to don leather mountain cy’s top exclusive nature and says Ley, and laughs. It was her scien- boots and Telemark skis and trudge adventure destinations: A se- tific interest in ecology that led her to across snowy, windswept slopes at sub- mester on Mo’orea, a small remote corners of the globe. zero temperatures to reach altitudes of tropicalT island in the South Pacific She has studied the biology of the up to 3,700 meters before heading off near Tahiti; several weeks on Guade- reef at Mo’orea, where the University of back home across country. “And all loupe in the Caribbean; three years out California, Berkeley maintains a re- that effort just to collect samples of and about in Hawaii’s national parks. search station, caught lizards for a proj- sand and gravel up there for our re- Next, a longer stay in Boulder, Colora- ect on Guadeloupe, investigated Ha- search,” adds Ley with a grin. do with regular high-alpine skiing and waii’s ecosystem ecology and analyzed An unusual project indeed. Especial- trekking in the Rocky Mountains. the microbial diversity of Mexico’s salt ly for a biologist whose focus, after Then on to an excursion to Mexico’s flats. “At that time I would have gone studying at the University of Califor- salt flats thanks to a NASA Fellowship anywhere for an interesting project – nia, Berkeley, had turned to the inter- and – as the icing on the cake – a sev- what I cared about most was working actions of living organisms with their eral-week Antarctic expedition. with people I could learn from,” says environment and to the investigation Ruth Ley, who has been a Director Ley. Little things like heat or cold have of microbes and their complex commu- at the Max Planck Institute for Devel- never put her off doing her research. nities. According to many scientists at opmental Biology since mid-2016, has English by birth, she learned to adapt the time, the ground in which Ley took seen a good bit of the world. Her pas- to new challenges at an early age and measurements and samples in summer sion for travel, however, has nothing to not to be easily deterred by obstacles. and winter alike was lifeless at extreme do with a jet-set lifestyle or a fondness She became a backcountry skier, for altitudes like those above the tree line for extreme sports. “To be honest, I instance, when her job as a biologist re- in the Rocky Mountains. It was widely
Photo: Jörg Abendroth/derphotograph.de should have been the last person to go, quired such skills. While working on believed that neither bacteria nor oth-
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Bacteria have colonized nearly every habitat on Earth. Ruth Ley visited some of them on her research expeditions. Above The scientist in one of Antarctica’s Dry Valleys. Right A piece of a bacterial mat from Mexico.
er microbes could survive the inhospi- snow, ammonia was being oxidized to she searched her soil samples for traces table conditions of frosty winters in form nitrate. Her previous scientific in- of bacteria and other kinds of life. sand or gravel under as much as 10 me- vestigations of Hawaiian soils had Success wasn’t long in coming. ters of snow. taught her that such a thing was possi- Thanks to her treks through snow and Ley’s research soon showed that this ble only if certain microbes were pres- ice, Ley was able to prove that high-al- was incorrect. She discovered that such ent. That’s why Ley went to the trouble pine soils aren’t lifeless at all; rather, regions did indeed present signs of life. of setting up her measuring equipment they are the permanent habitat of nu- Measurements showed that, some- between the sand and snow high up in merous species of bacteria. For her doc-
where between the ground and the the mountains. Back in the laboratory, toral thesis, she identified microbes Photos: Private collection (2)
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The decision to conduct research at a medical faculty » was one of the best I ever made in my career.
that, protected from cold by the thick thing that made her stand out (she had microbes that, numbering in the mil- snow cover, are also active in winter – continued to speak English with her lions, colonize the human body as per- thus contradicting some of the theories parents through the years). She was also manent inhabitants of the skin and di- held by geologists. confronted with differing status sym- gestive tract. One thing we can already bols and eating habits. A small exam- say for sure is that microbiome research RAISED WITH CULTURAL ple? Ruth Ley thinks for a moment. is shedding new light on unexpected DIFFERENCES “Baguette and Camembert would be relationships that control our bodies. one. In Paris that’s a simple lunch for Ley’s courage in challenging old certain- normal working people. In California it UNKNOWN LODGERS ties and exploring new territory isn’t has the aura – who knows why – of a surprising. At the age of six. she moved high-society lunch.” Together with other researchers, Ley with her parents and two sisters from She made similar observations at was able to show for the first time that Surrey in the UK to Paris. Her father was school. In France you addressed your the human microbiome is much more an engineer and had been offered an at- teachers quite naturally using the po- than just a collection of stowaways that tractive post there. That left the daugh- lite vous form, or as monsieur or ma- help break down food into usable com- ters little choice but to rapidly adapt to dame. In the US, students and teachers, ponents. In fact, the myriad microor- the new environment and learn the un- so it appeared at first glance, were sud- ganisms in the intestines play a crucial familiar language as quickly as possible. denly on the same level. Everyone used role in our health and contribute, for Seven years later came the next the egalitarian English “you,” and instance, to obesity, diabetes and change. Ley, now 13 years old, had teachers were simply “Bob” or “Jane.” chronic autoimmune disorders. Medi- grown to feel very much at home in her But Ley quickly realized that appear- cations, in turn, can have deleterious new country, and spoke only French ances could be deceptive. Despite the effects on the microbiome. with her friends and sisters. Once again, seemingly more relaxed rules, Ameri- The individual intestinal microbio- the move was due to her father’s job. can kids had, to her amazement, much ta each of us possesses depends on This time it was to another continent – more respect for authority in school. where we have been in life, as we don’t from Europe to Palo Alto in California’s “In Paris, kids made off with anything pick up microbes until we are born. Be- Silicon Valley. Again she discovered that that wasn’t nailed down. I never expe- fore then, our intestines are thought to both school and everyday life followed rienced that in California.” be sterile. The first bacterial species to completely different rules than before. Without doubt, such radical and op- populate the intestines come from a “It was difficult adjusting,” Ley re- posing cultural habits take some get- newborn’s immediate environment calls. “France and the US are culturally ting used to. But experiencing early on and are composed of maternal vaginal, very different.” Once more, she and her in life that it’s worth being open to new gut and skin bacteria. Little by little, sisters had to learn new daily “codes” ideas and examining things carefully other species of bacteria from the envi- of behavior. Things that were normal stands you in good stead for a life pio- ronment are added. The microbiome’s and common in one country, Ley dis- neering a completely new scientific dis- community composition at any given covered, were considered snobby and cipline. Ruth Ley is now in the van- time depends primarily on our diet, but elitist in another – and vice versa. Ley’s guard of a field of research that has also on many other factors. This means British accent, which to the ears of her been expanding at a breathtaking pace the microbiome of each individual, American schoolmates initially made over the last few years. Her aim is to de- each family and each human popula- her sound pretentious, was the first code the microbiome: the collection of tion can have a distinct composition.
2 | 17 MaxPlanckResearch 49 In Tübingen, Ruth Ley aims to investi- advances have been critical. First, the gate how genes, the immune system and composition of the intestinal microbi- environmental factors affect the human ome can now be determined using microbiome. The intestinal bacterium Escherichia coli (right) is an infrequent molecular biology methods, eliminat- member of this bacterial community. ing the need to culture the bacteria in Most strains are harmless, but some can the laboratory. In addition, modern se- also trigger infectious diseases. quencing techniques now enable us to rapidly decode the genetic composi- tion of microbes, and computer anal- ysis of data has accelerated tremen- dously.
USING MICE WITH NO INTESTINAL FLORA AS A MODEL
In the early 2000s, researchers from Washington University in St. Louis Medical care also plays an important “Essentially, we’ve known for a long (USA) working with clinician Jeffrey role in our intestinal microbiota. After time that certain bacteria in the human Gordon investigated the link between only one week of antibiotics, for exam- intestinal tract are very important for obesity and gut bacteria using germ- ple, the composition and activity of the the body,” explains Ley. “Despite this, free mice. Raised from birth in a bacte- microorganisms alters dramatically. we knew very little about most of them ria-free environment, these animals Dozens of species may disappear and until the early 2000s.” The reason was have no intestinal microbiota of their others take their place. Measurements that most of these microscopically own. This makes them an ideal model show that many of the approximately small organisms couldn’t be investigat- for elucidating the influence of specif- 2,000 chemical metabolic products ed in the lab, as we weren’t yet able to ic members of the microbiome on commonly found in feces – a sort of fin- grow them in culture dishes using arti- health. With microbiota-free mice, sci- gerprint for bacterial activity – change ficial nutrient media. entists are able not only to precisely temporarily in concentration following “But microbiome research has ex- control the type of food they are given,
antibiotic ingestion. ploded since 2004,” says Ley. Several but also to administer selected intesti- Photo: Jörg Abendroth/derphotograph.de (top), Jürgen Berger/MPI for Developmental Biology
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Number of various types of microorganisms: 1000 on the skin 600 in the mouth, throat and respiratory tract 25 in the stomach
500–1000 in the small and large intestines
Humans offer microorganisms a 60 home in a variety of organs, including in the rectum the respiratory tract, the skin and the gastrointestinal tract.
nal bacteria to test the effects of the mi- the process of applying techniques possess no intestinal bacteria of their crobes and of differing diets on individ- from Ley’s specialty field – environ- own normally have extremely little ual functions of the body. mental microbiology – to research into body fat. That changed abruptly when Just when Gordon’s team started to the microbes of the human digestive they were colonized by gut microbiota. sequence the genome of gut bacteria, tract. Ley therefore left him a message Even though the mice ate no more food Ley joined the team. It was a decision one day asking if he needed a microbi- than before, their fat stores grew. that proved fortuitous for a number of al ecologist. After visiting and inter- Shortly afterwards, Ley was able to people. Ley had already met a research viewing with Gordon and his group, demonstrate another connection be- colleague who would go on to become she joined as a postdoc in fall 2004. tween microbes and body weight in a her life partner. Lars Angenent, a suc- clinical weight-loss study involving 12 cessful Dutch bioprocess engineer, had MICROBIOME MIXTURE AFFECTS obese individuals. The results showed been working at the same university as BODY WEIGHT that, similar to mice, obese and nor- Ley in Boulder. Soon afterwards, how- mal-weight people can have different ever, he was offered a position as an as- A short time later, Gordon’s team pub- mixtures of bacteria in their intestinal sistant professor at Washington Uni- lished a groundbreaking paper. For the tract. The most marked difference was versity in St. Louis, while Ley stayed first time in medical history, the scien- in the proportion of the two most on at the University of Colorado. The tists were able to show that – contrary common representatives of intestinal couple traveled back and forth be- to long-held belief – our body weight bacteria, the Firmicutes and Bacteroide- tween the two cities for several years – is by no means solely dependent on tes phyla. Obese individuals enrolled and for much of that time with no how much we eat and how much en- in this study, Ley found, had signifi- prospects of ever being able to live in ergy we expend through exercise. A cantly more Firmicutes and fewer Bac- the same place. third factor, the microbial composition teroidetes than normal-weight people, Then they had a sudden stroke of of our intestines, is involved. and their microbiomes came to resem- fortune. Ley discovered that Gordon’s The researchers employed an ele- ble those of the lean controls more as team in the medical faculty of Wash- gant trick to prove this. They trans- they lost weight. ington University offered the perfect ferred the intestinal microbiome of Gordon’s team then went one step working environment for somebody conventionally raised laboratory mice further. This time they transferred in- with precisely her expertise. Not only to germ-free mice. Despite having un- testinal microbiomes from normal- was Gordon’s laboratory large and suc- limited access to food, the animals that weight and from genetically obese lab-
Graphic: Science Photo Library cessful; he and his colleagues were in are kept in sterile conditions and that oratory mice into germ-free mice. The
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THE BEST VOGEL CONVENTION CENTER BACKDROP IS WÜRZBURG’S INNOVATIVE EVENT LOCATION
Left Bacteria are essential for effective digestion: More than half of human feces consists of excreted intestinal bacteria. Above The composition of the bacterial community also affects body weight: Obese mice have more Firmicutes bacteria than Bacteroidetes; this relationship is reversed in animals with a normal body weight.
results were clear: mice that had been of the variation in the microbiome is biome research program over the next germ-free and had been given a micro- due to our genes. few years. She is currently also expand- biome from obese rodents became fat- Last but not least, Ley’s crossover to ing her laboratories as well as forming ter than those that received microbi- biomedical research had another fruit- new joint research teams involving the omes from lean donors. ful outcome for her and Angenent, who Institute and the Faculty of Medicine at The result electrified the whole is now her husband. Since their time in the University of Tübingen. team. For the first time, researchers had St. Louis, the two researchers have not One special focus of her future re- been able to demonstrate that a pro- only started a family – their son is now search will be performing large-scale pensity for obesity could be transferred 10 years old – Ley and Angenent have studies to sample microbes from the in- from one animal to another – simply since also succeeded in planning their testines of individuals from different Where once printing presses churned noisily, advanced acoustic wall by manipulating the mixture of the mi- career moves from post to post togeth- backgrounds. Using these samples, she crobiome in their gut. “It was one of er. In 2008, Ley moved with her hus- aims to investigate what effects genes, systems and silent air conditioning now ensure that even the finest notes those ‘Oh my God!’ moments. We were band and son to Ithaca, New York, the immune system and environmen- can unfold their magic to full effect. Against a backdrop of spacious absolutely elated,” Gordon told a re- where they continued their work at Cor- tal factors have on human intestinal porter. Ley, too, found her time in Gor- nell University. In 2013 she became an microbiota. As Angenent has taken up industrial architecture, you can take advantage of more than 4,000 square don’s team to be a particularly inspir- associate professor in the Department of a position as a Humboldt Professor in metres of event space to mount even the most spectacular of concepts, ing experience: “I never thought I Molecular Biology and Genetics. the Department of Geoscience at the would be applying for a job at a medi- At the Max Planck Institute in Tübin- University of Tübingen, their shared turning our VCC into an amazing changing stage that opens up cal faculty, but that decision was one of gen, Ley plans to establish a new micro- life as researchers can now continue. the best I ever made in my career.” undreamt-of possibilities.
FAMILY AND CAREER Let your imagination run free and contact us. GLOSSARY Among other things, the large number We will be happy to assist you at any time. of groundbreaking papers she has pub- Microbiome: The totality of all microorganisms that inhabit a living organism. Humans, for instance, are home to 10 times more microbes than their bodies possess cells. lished in the last few years testifies to It is estimated that each of us is inhabited by approximately 100 trillion bacteria. Most this. She discovered, for instance, that of these live in the intestines, but we also have lodgers on our skin, in the oral and nasal the intestinal microbiota changes dras- cavities, and on our sex organs. There is frequently a symbiosis between humans and tically during pregnancy, which im- microbes, benefiting both. Some bacteria, however, are only “table companions”, nei- pacts the mother’s metabolism and ther harming nor helping. thus ensures the optimal provision of Firmicutes/Bacteroidetes: Two phyla of bacteria, usually with differing cell wall struc- nutrients to the fetus. Just as signifi- tures. Firmicute bacteria convert fiber into short-chain fatty acids that the body can absorb. The Bacteroidetes phylum, in contrast, breaks down complex polysaccharides. cantly, Ley worked on identifying hu- Together they account for the majority of the intestinal microbiota. man genetic determinants of the mi-
crobiome – in other words, how much Photo: Science Photo Library/Gschmeissner, Steve; graphic: MPG
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VCC_AZ_englisch.indd 1 15.03.17 10:55 THE BEST VOGEL CONVENTION CENTER BACKDROP IS WÜRZBURG’S INNOVATIVE EVENT LOCATION
Where once printing presses churned noisily, advanced acoustic wall systems and silent air conditioning now ensure that even the finest notes can unfold their magic to full effect. Against a backdrop of spacious industrial architecture, you can take advantage of more than 4,000 square metres of event space to mount even the most spectacular of concepts, turning our VCC into an amazing changing stage that opens up undreamt-of possibilities.
Let your imagination run free and contact us. We will be happy to assist you at any time.
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VCC_AZ_englisch.indd 1 15.03.17 10:55