50 years Biozentrum Life Sciences - Universität Basel
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
50 years Biozentrum Life Sciences
Foreword ––– 3
Dear
readers
“Pioniergeist” – pioneering spirit – was the word that
defined the launch of the Biozentrum 50 years ago. The
groundbreaking idea was to bring together outstanding
biologists, chemists and physicists under one roof and
trust that they would determine how molecules generate
life. Looking back, we can say that the Biozentrum has
fulfilled and even exceeded these expectations: The
institute has made transformative discoveries, spawned I was seven years old and lived in Birsfelden when the
several Nobel Laureates, and trained thousands of Biozentrum was opened, and I still remember the excite-
students and scientists to become leaders in academia, ment that surrounded the new institute in our region.
biotech, business and society. Now 50 years later I again feel the same enthusiasm and
“Pioniergeist”, because the Biozentrum has reinvented
Many ingredients have contributed to the Biozentrum’s and rejuvenated itself. The 1971 founders have been
success: A visionary mission and the freedom to address followed by a new generation that is as passionate and
fundamental questions in biology; the generous support driven as their predecessors. And the move into our
by university, government, industry and the public; and brand-new building will support cutting-edge research for
Basel’s cosmopolitan culture and belief in the common years to come. In another 50 years the Biozentrum will
good. But as you will read in this brochure, the main be renewed once again. In the words of Bob Dylan, the
ingredient has been the people who have studied, Biozentrum will stay “Forever Young”.
researched and worked here. The Biozentrum became a
magical place through creative and ambitious colleagues May your hands always be busy
who brought their curiosity and passion from all over the May your feet always be swift
world to Basel. So while we celebrate the 50th anniver- May you have a strong foundation
sary of the Biozentrum vision or the 50th birthday of the When the winds of changes shift
Biozentrum building, we are truly celebrating 50 years of May you build a ladder to the stars
world-class Biozentrists – researchers, students and staff. And climb on every rung
May you stay forever young
Professor Alex Schier
Director of the Biozentum, University of Basel
Contents 58 Pioneering spirit
meets research
60 Biozentrum highlights 1971 – 2021
8 Biozentrum’s golden jubilee
64 It started with a spark
12 A beacon of science
68 “Feuersucher” by Gottfried Schatz
70 Studying phages
72 An eye on the future
16 A fascination 76 A springboard for top researchers
for research
22 A quantum of knowledge
25 Unlocking the mystery of life
26 “It’s not just about minor details, but rather
about fundamental questions”
30 Tracking virus evolution
32 The greatest challenge remains the 80 Pioneers of new
human brain
36 New approaches in the fight against bacteria knowledge
38 A stem cell researcher to the core 82 The pioneer of genetic engineering
40 50 years of research at the Biozentrum 86 The tale of the king and his servants
42 State-of-the-art technology 88 Other prestigious awards for Biozentrum professors
46 Behind the scenes 90 Spectacular moments in evolution
48 Facts and figures 92 “It was an incredibly exciting time”
94 A hisTORic breakthrough
98 A bundle of nerves
50 Between lecture
hall and lab 102 In the service
52 Studying at the cutting edge of research
of research
54 Nurturing outstanding young researchers
104 Electron beam meets molecule of life
107 What nuclear spin can tell us
108 “A virtually endless domain”
109 Bioinformatics – life sciences in the dry lab
“For 50 years, we have been studying the mystery of how molecules and cells create life.”
The Biozentrum’s golden jubilee ––– 8 The Biozentrum’s golden jubilee ––– 9
Biozentrum’s
golden jubilee Greeting: Andrea
Schenker-Wicki, President
of the University of Basel
Was it the driving force of a handful of Basel personalities?
Was it the excellence of the University’s researchers?
Or was it the exceptionally healthy public finances that
made the opening of the Biozentrum possible 50 years
ago? A look at the history of the Biozentrum’s origins
offers an answer, which can be expressed very simply:
It was, without question, a huge stroke of fortune – for The new Biozentrum building represents a key milestone on the path to the University of Basel’s Life Sciences Campus.
Further new buildings are planned in the immediate vicinity of the University Hospital and the University Children’s Hospital on
science, for business, and for the region’s inhabitants. the Schällemätteli Campus. These will provide premises for the Department of Biomedicine, the Natural Sciences and for ETH
Zurich’s Department of Biosystems Science and Engineering (D-BSSE). Almost 800 million Swiss francs are being invested
in cutting-edge infrastructure for the Life Sciences Campus in order to provide the optimal conditions for research and teaching.
The late 1960s were a time of great upheaval in biology Between the laboratories of the Faculty of Natural Sci- the region’s prosperity. Year on year, our sponsoring cantons invest many hundreds of millions of Swiss francs in our
and medicine. New findings allowed researchers to ences and the University Hospital, a seven-story building University, enabling us to provide higher education of the highest quality and compete among the top hundred research
fathom the molecular mechanisms behind life processes. was erected and tailored to the needs of cutting-edge universities in the world.
While the US and the UK played a leading role, Basel too biological research: interdisciplinary collaboration, flat
was quick to realize that this was an area with great poten- hierarchies rather than empires, and research groups rath- The achievements of the Biozentrum over the last half century have played a key role in cementing our reputation as
tial – and one in which it had some catching up to do. er than teaching chairs. And as the Biozentrum attracted one of Europe’s top locations for the life sciences, and broadcasting this reputation to the world. With the new Biozentrum
some of the world’s finest researchers, English was building – as controversial as its genesis may have been – our sponsors demonstrate the same courage and belief in the
The founding of the Biozentrum can be attributed to adopted as a lingua franca – an unprecedented move in future that distinguished its founders 50 years ago. In the name of the University of Basel, I am grateful for the trust
a number of courageous, visionary personalities from the Swiss academic world at the time. placed in our institution, and hope on behalf of us all that this success story will continue for many chapters yet.
research, politics and industry who recognized a combi-
nation of favorable circumstances: a prevailing spirit of We are immensely grateful to be moving into new prem-
optimism in the region, the population’s confidence in ises this year, half a century on from the Biozentrum’s
progress and the future, an industrial sector with money foundation. The University of Basel is proud of its spon-
to spend on non-profit initiatives, and a generous Basel sors – the cantons of Basel-Landschaft and Basel-Stadt,
parliament with a government receptive to new projects. which believe in the University and its importance to
The Biozentrum’s golden jubilee ––– 10 The Biozentrum’s golden jubilee ––– 11
Professor Pascale Cossart,
Dr. Jörg Reinhardt, Chairman of Novartis, Basel Institut Pasteur, Paris, France
“Since its inception half a century ago, the Biozentrum has evolved into a vital part
“Participating in the Scientific Advisory
of Switzerland’s pharmaceutical and medical ecosystem, both as a research hub as
Board has been a fantastic experience.
well as a center of educational excellence. As part of our efforts to boost interdis-
Science at the Biozentrum is superb
ciplinary research and strengthen collaboration with academia, Novartis is proud
and so wide open to novelty and new
to have established strong ties with the institute in areas such as structural and
horizons. The SAB composition was ter-
molecular biology as well as fundamental research into diseases such as cancer, Professor Paul Nurse, Nobel Prize rific! Interactions with young and older
among others. I am convinced that this spirit of innovation will form the basis of Laureate, Director of the Francis scientists was great. Coming to Basel
successful collaborations in the future.”
Crick Institute, London, UK was a pure pleasure. I miss it!”
“The Biozentrum is a jewel in the crown of
Swiss science. It was a powerhouse at the birth
of molecular biology and continues to be an
outstanding institution of excellent science.
Dr. Severin Schwan, CEO of Roche, Basel Happy 50th birthday Biozentrum!”
“Many great minds have led to the outstanding success
of the Biozentrum since its founding 50 years ago. We’re
proud to note that one of the original initiators of the
now world-renowned Biozentrum was Alfred Pletscher,
Roche’s head of research at that time. Research-driven
companies today enjoy the fruits of basic research done
decades ago. The Biozentrum and other leading institutes
Professor Catherine Dulac, Howard Hughes Medical
will remain key to medical breakthroughs in applied
research.” Institute, Harvard University, Cambridge, USA
“The scientific creativity and productivity at the Biozentrum over the last
50 years have been nothing short of extraordinary. The remarkable scholar-
ship and motivation of Biozentrum scientists and the outstanding diversity
and quality of their scientific endeavors make the Biozentrum a towering
institution in Europe and in the entire world. I wish the Biozentrum another
50 years of stellar accomplishments!”
Dr. Vas Narasimhan, CEO of Novartis, Basel
“Basel and the Rhine Valley have a rich history in life
sciences and biomedical innovation, and the Biozentrum
has helped carry that legacy forward, taking the visionary
step 50 years ago to develop an interdisciplinary research
facility. Your work to mold the scientific minds of tomor-
row embodies the spirit of innovation and commitment
Professor Randy Schekman, Nobel Prize Laureate,
to science-based progress that have helped improve our
world for generations—and that will keep humanity on a University of California, Berkeley, USA
path of progress for generations to come.” “In 1982 and 1983, my family and I were hosted by Professor Gottfried Schatz for a
abbatical year William Wickner and I spent in his lab. The year was enriching in so
many ways, including the birth of my daughter in Basel that fall. My best to all the
members of the Biozentrum on this jubilee celebration.”
New Biozentrum building ––– 12 New Biozentrum building ––– 13
A beacon of
science Text:
Evi Sonderegger
architecture as the infrastructure that stops you in your
tracks. “Molecular biology research places the highest
demands on energy, cooling, temperature stability, vibra-
tion-free and pressure conditions, biosafety and much
more. Since we have a broad spectrum of research, the
needs of our various groups and technology platforms
vary considerably,” explains Roger Jenni, Head of Tech-
nology and Logistics, who has been closely involved in The top levels offer breathtaking views of the Basel
the project from the beginning. “The new building is a region and the Life Sciences Cluster. Over the next few
A new highlight has been added to the Basel skyline: the truly remarkable feat of advance planning in terms of all years, many of the University of Basel’s Life Sciences
recently completed 73-meter Biozentrum tower by the the technical conditions it will have to meet in future,” he sites dotted around the city will be brought together in
architects Ilg Santer. When the sun shines on its chrome concludes with unconcealed pride. Biozentrum director Of the building’s 19 levels – 16 above ground and three the Life Sciences Campus. This physical proximity will
steel and glass facade, the building is transformed into Professor Alex Schier also considers the new building to below – ten will be devoted to research projects compris- further boost synergies among different projects.
a beacon in the visual as well as the figurative sense. be a beacon, externally as well as internally: “The move ing around 400 employees, along with the research facil-
Stepping into the three-storey entrance hall with its to our new cutting-edge home is a significant milestone ities in the basement levels. Adjacent floors are joined
design structure inspired by water lilies invariably elicits a for us. Thanks to the state-of-the-art infrastructure, we through an open staircase and a meeting zone benefitting
reverential “wow.” The foyer offers an exciting contrast to remain competitive on the global academic stage and can scientific exchange because especially in interdisciplinary
the functional layout of the laboratory tower, providing an attract the world’s best scientists to Basel.” research – the bedrock of the Biozentrum – innovative
attractive social space with its freely accessible outside ideas often arise from random discussions. This idea is
area complete with seating and water features. This is also behind the decision to distribute shared technology
where the paths of researchers, visitors and up to 900 platforms throughout the different levels, as well as the
students on their way to and from the adjacent lecture transparency that permeates the architectural design of
halls and seminar rooms cross in lively interaction. the research levels: even the few dividing walls are made
On the research levels and in the sensitive scientific of glass, giving desk workers unimpeded views of work
facilities in the basement levels, it is not so much the unfolding in the lab.
New Biozentrum building ––– 15
Autor: Vorname Nachname Life Sciences ––– 3
Research
A fascination
for research
Since its foundation, the Biozentrum has been passionately
devoted to studying molecules, cells and organisms to achieve
a deeper understanding of the fundamental principles of life.
This pursuit transcends the boundaries between research fields
or countries, as the overlap between completely different disci-
plines is often where innovative ideas and research approaches
are most likely to emerge.Research ––– 22 Research ––– 23
A quantum of Driven by curiosity
At the time, neither the Nobel Committee nor Einstein
himself imagined how society might benefit from quan-
A universal switch for cell growth
After testing rapamycin on yeast cells, Hall and his team
discovered a kind of universal on/off switch for cell divi-
knowledge
tum theory or the photoelectric effect. This wasn’t felt to sion. It was a protein they dubbed “TOR” (short for “target
be a major concern: The important thing was that the the- of rapamycin”). Rapamycin essentially acted as the finger
ory explained a natural phenomenon, as well as offering that flips the switch. Further tests revealed something
an extensive toolkit that could be applied to numerous even more astonishing: TOR did not actually control cell
other physical observations and fields of research. division, as they had assumed, but cell growth.
For the uninitiated, basic research can sometimes be hard to This kind of research, driven solely by curiosity, is known “The accepted wisdom at the time was that cells simply
as basic research. Unlike applied research, its aim is not grew whenever sufficient nutrients were available,” Hall
comprehend. It asks questions that have little to do with everyday to produce an immediate benefit for society; it is solely explains. “That moment was a dream come true for us.
life, and although it ultimately leads to new knowledge, this concerned with expanding human knowledge. That said, We had discovered an entirely new field of research.”
sooner or later most basic research inevitably yields Nevertheless, outside of Hall’s research group the discov-
knowledge is generally of no immediate use to humanity. some kind of practical benefit. “There will always be a ery was met with very little enthusiasm. When they tried
Nevertheless, one thing is clear: Without basic research, we need for basic research. Not to support it would be a fatal to publish their results in 1994, the study was rejected
mistake,” says Professor Michael Hall, a cellular biologist seven times by various scientific journals. A year passed
would still be stuck in the Stone Age. at the Biozentrum. before the results were finally printed.
Text:
Atlant Bieri His career is a prime example of how ostensibly “useless” From knowledge to application
basic research can suddenly open up a broad array of Since then, TOR has shot to fame as a control switch for
potential applications. Working at the Biozentrum in the cell growth, with far-reaching implications for applied
1980s, he studied substances that suppress the immune research. “We now know that TOR plays a key role in
system. These substances are deployed to great effect in numerous diseases like cancer or diabetes, as well as
transplant medicine, preventing the immune system from biological processes such as aging. The pharmaceutical
In the year 1905, a 26-year-old theoretical physicist sat in Concluding that the wave model was inadequate, the rejecting the foreign organ. One of them was rapamycin. industry has jumped on the bandwagon, and is using
his room in Bern, deep in thought. The problem he was young physicist mentally divided the waves into tiny “It prevented the division of immune cells, thereby di- the discovery to search for new treatment strategies
mulling over concerned the nature of light. For several pieces and named them “quanta.” He imagined these minishing their effectiveness. There was just one catch: and life-prolonging drugs.”
decades, it had been known that shining light on two quanta as small packets of energy, the intensity of which no one understood exactly how the substance acted on
metal electrodes would result in a voltage that could depended solely on the light’s wavelength, rather than cells. Our goal was to find out,” says Michael Hall. And what became of Einstein’s photoelectric effect?
become strong enough for a spark to jump across the how many of them there were. Under this model, if a Over the next hundred years, his groundbreaking theory
gap. The light somehow had the effect of electrically sufficiently charged light quantum encountered a metal, laid the foundations for the development of the solar
charging the metal – the renowned photoelectric effect. it could dislodge an electron. If the light quantum was panels that power pocket calculators, houses, satel-
Paradoxically, the charge was not affected by the intensity too weak, however, the electron would stay put. This lites and space shuttles. The same principle also paved
of the light, but only by its frequency. At the time, no theory, which was repeatedly confirmed by experiments, the way for the light sensors used in alarm systems
explanation could be found for this observation. Light earned the physicist the Nobel Prize in 1921. His name or garage and elevator doors. So if you still doubt the
was thought to consist of a series of waves, so it was was Albert Einstein. importance of basic research, next time you’re in a high-
assumed that the more light there was, the greater the rise building feel free to take the stairs!
number of waves hitting the metal, and therefore the
stronger the effect. This was not the case, however.Research ––– 24 Research ––– 25
Fighting cancer with bacteria Nanotech for cancer diagnosis
The idea for an application or the creation of a Meanwhile, the spin-off ARTIDIS is devoted to
start-up often has roots in findings from basic refining atomic force technology for cancer diag-
research. This was also the case for the Biozen- nostics. The company was formed by Biozentrum
trum spin-off T3 Pharmaceuticals. Founders Simon researchers in 2014. ARTIDIS stands for Automated
Ittig, Christoph Kasper and Marlise Amstutz did Reliable Tissue Diagnostics. The centerpiece of
research on bacterial nano-syringes at the Bio- their solution is an atomic force microscope that
zentrum, initially as doctoral researchers and later can be used to inspect surface features.
as postdocs. These structures, known as type III
secretion systems, are used by bacteria to import The founders of ARTIDIS, led by Marija Plodinec
foreign proteins into cells. and Marko Loparic, found an entirely new applica-
The team made use of this feature to develop a
new generation of cancer treatments, reprogram-
ming the bacteria to selectively inject therapeutic
tion for this nanotechnology: they use it to “probe”
cancer cells, which exhibit a lower degree of
stiffness than healthy cells. This enables them to
create nanomechanical profiles of biopsies that
Unlocking the
proteins into cancer cells, either killing them or
activating the immune system in a particular way.
It is the first cancer treatment to directly suppress
tumor growth by using live bacteria and their
shed light on whether they are cancerous, whether
they are malignant, or how aggressive a particular
tumor is. The new diagnostic tool could enable
oncologists to find the optimum treatment for their
mystery of life Text:
Katrin Bühler
nano-syringes. The first clinical trials are due to patients faster in the future. The practical feasibility
start soon. The start-up’s innovative approach has of ARTIDIS is currently being tested in collaboration
been enthusiastically received by investors and with several hospitals. Contemplating everything that is immune system? How does a stem What motivates and drives them
foundations as well as researchers and clinicians. happening at this very moment in cell know what it is supposed to is the prospect of creating new
At the Falling-Walls Conference in Berlin in 2018, each cell of our body is guaranteed become? And how does a healthy knowledge with their research and
T3 Pharmaceuticals was proclaimed “Science to inspire a sense of awe. Cellular cell turn into a cancer cell? contributing to a greater whole with
Start-Up of the Year.” copying machines faithfully transcrib- their discoveries.
ing genetic material, countless ribo- United under the umbrella of the
somes tirelessly producing proteins, Biozentrum, researchers tackle dis- In the following pages, eight Bio-
mitochondria providing the energy to ciplines as diverse as neurobiology, zentrum researchers share what
power it all, cells import and export cell biology, developmental biology, fascinates them about their work.
molecules and they communicate infection biology, structural biology, Their conquest of uncharted territo-
with their neighbors – the body is biophysics or computational and sys- ries is facilitated by the Biozentrum
like a bustling city that never sleeps. tems biology. With over 30 research Technology Platforms and Services
groups and staff from around 50 teams.
This dazzling array of vital processes nations, it brings together a variety
is reflected in the diverse range of of expertise, perceptions, expe-
questions posed by researchers rience, approaches and forms of
working at the Biozentrum. What creativity. This has been its strength
exactly happens inside a cell? How for the last 50 years. What all these
do genes regulate the intricate researchers have in common is their
biochemical machinery? How do fascination for the single overarch-
neurons communicate with each ing question: “How do molecules
other and how does the brain control and cells create life?” With tireless
our movements? Why do we sleep? curiosity and limitless ingenuity, they
How do viruses spread? How do are committed to solving this puzzle
bacteria stay under the radar of our one piece at a time. Together.Research ––– 26 Research ––– 27
“It’s not just
about minor details,
but rather about
fundamental
– Prof. Timm Maier and Professor Maier, Professor Hondele, question and wants to know what
Prof. Maria Hondele perhaps not everyone has a very the structure of a particular protein
clear picture of what is meant by looks like so as to better under-
structural biology. Can you explain stand its function in the cell.
questions”
briefly what this field is all about?
Maier –– Of course! We examine What methods do you use?
the structure of all the constituent Maier –– Fortunately, we are no
parts of living organisms at an longer solely dependent on X-ray
incredibly high resolution, which crystallography, which requires pro-
Interview: allows us to distinguish the indivi- teins to be crystallized before they
Yvonne Vahlensieck dual building blocks and structural can be studied. Increasingly, our
principles. We do this not just to primary tool is electron microscopy,
find out what something looks which we can use to observe larger
like, but also to understand how it complexes. We can also combine
works. We investigate mechanistic individual still images to produce
Structural biology operates at the very smallest scale, principles that apply in the fields animations that show us how mo-
of neurobiology, infection biology – lecules twist and turn. Molecules
investigating how molecules interact inside cells. Researchers at everywhere, in fact. engage in some really remarkable
the Biozentrum pursue this goal with the help of cutting-edge Hondele –– Structural biology feats of yoga.
requires highly developed technical
technology. Just as important, however, is lively collaboration knowledge. Not many groups have
between research groups – as Professor Maria Hondele and this knowledge, so collaborations
are frequent. For instance, someone
Professor Timm Maier explain. approaches Timm with a biologicalResearch ––– 28 Research ––– 29
Which structures are you currently What should researchers looking to
researching, Professor Hondele? join your groups bring to the table?
Hondele –– We have known for Maier –– The most important thing
some time that membranes play a really is a passion for problem-solv-
key role in the organization of cells. ing. Also, the creativity to find the
Over the last ten years, however, it right approach, often against the
has become apparent that proteins advice of others. Forging new paths
and nucleic acids are also capable Professor Maier, what are you also takes courage, however. And of
of self-organization without the working on? course the ability to think logically
help of membranes. We replicate Maier –– We want to understand and analytically so as to properly
membraneless organelles of this how metabolic processes are interpret results.
sort under the microscope, and try controlled in human cells. The Hondele –– Definitely. I also think
to understand the biophysics behind conversion of nutrients into energy a certain tolerance for frustration
them. There is no set of Ikea-style or different cellular components is is relatively important. In addition,
assembly instructions to follow; an essential process. For example, you have to be able to take a large
these are highly dynamic processes. we study lipid metabolism in higher Professor Hondele, you only came number of ideas and filter out just
The big question is then, of course, organisms, which is involved in the to the Biozentrum around a year the most exciting or important ones.
what function these structures per- onset of numerous diseases such ago. How have you found it so far? Above all, however, you should find
form for the cell, and how they are as cancer or diabetes. The proteins Hondele –– The Biozentrum is one out what you’re really good at. After
regulated. that we study work much like tiny of only a few institutes in Switzer- all, there are many different ways of
computers. They receive various land that brings together a variety of doing research.
You are working in an area the signals, process them, and regu- biological disciplines under one roof Maier –– Exactly. A part of what
importance of which has only late the production of new cellular at such a high level. This is naturally we do is finding the right person for
become clear in the last few years. components. very conducive to forming collabora- the right project. Some people invest
Do you see yourself as a pioneer? tions and tackling research questions three or four years of their life in a
Hondele –– It is rather special to It must be thrilling to make these beyond one’s own area of expertise. particular topic. It’s very impor-
be working in such a new field. normally invisible processes It’s also just a lot of fun to be around tant that their hard work leads to a
Sometimes one shines new light on visible... so much fantastic research. The reward – not in the form of money,
established truths, which can ruffle Maier –– Yes, there is something facilities, with their outstanding but of satisfaction.
some feathers on occasion. There is very special about the moment equipment and expertise, are an ex-
definitely a certain sense of heading when you see a protein structure tremely helpful resource that opens
into the unknown. It’s not just about for the first time, and perhaps even up new technological possibilities
minor details, but fundamental ques- hold it in your hands as a 3D-printed for us. They allow us to become
tions with likely implications for cells model. much more creative in our research.
at many different levels.
Do you have any plans for joint What else have you been particu-
projects? larly impressed by?
Hondele –– (laughs and gestures at Hondele –– The open-door policy,
the board on her door, which is cov- and how it has become second na-
ered with sketches for experiments) ture to the students and postdocs!
Maier –– I expect that we’ll work I have often had someone from a
together a great deal. For one thing, different group come into my office
there is some overlap in terms of looking for advice on a research
the techniques we use, which could question. I think that’s great.
be helpful for Maria’s research
questions. On the other hand, Ma-
ria’s experience will certainly be of
help in understanding highly mobile
proteins.Research ––– 30 Life
Forschung
Sciences–––
–––31
3
“Putting the results
of research that is
ultimately paid for
by the taxpayer
behind a paywall is
simply the wrong
Tracking virus approach.”
– Prof. Richard Neher
evolution Text:
Yvonne Vahlensieck
“Nextstrain was What Professor Richard Neher is really interested in is evolution. He wants
to find out whether it can be predicted. His efforts to this end include sifting
originally a pure- through the gene sequences of influenza viruses from the last two decades
ly academic pro- in search of patterns. As a result of this research project, in 2020 he unex-
pectedly found himself at the center of the COVID-19 pandemic as a member
ject. Our vision of the Swiss National COVID-19 Science Task Force and an expert in high
was to create a demand by the media. “As we have been studying the evolution of RNA
viruses for years, we were in a very good position to assess the situation
current family from the outset,” he reports.
tree of influenza Making science publicly accessible
A key role in fighting the pandemic has also been played by the online plat-
viruses online.” form Nextstrain, which Richard Neher developed several years ago with a The success of the Nextstrain platform is not just due to how it presents com-
colleague. The application tracks mutations in the genetic material of the plex information in an easily understandable format – it also offers free access
– Prof. Richard Neher SARS-CoV-2 virus and provides a graphic visualization of its spread around the to the underlying code and data. This earned Richard Neher and his colleague
world in real time. This helps decision-makers to promptly develop suitable the Open Science Prize, a distinction awarded to projects that help make
measures to fight the pandemic. Neher is unable to make predictions about scientific data publicly available online – something for which Richard Neher
the future evolution of the SARS-CoV-2 virus, however. We simply don’t know has been campaigning for a long time: “Putting the results of research that
enough about the virus and how it interacts with humans yet. is ultimately paid for by the taxpayer behind a paywall is simply the wrong
approach.”
“Nextstrain was originally a purely academic project,” he explains. “Our
vision was to create a current family tree of influenza viruses online.” Yet, the In future, Richard Neher hopes to shift the focus of his research toward bac-
platform was soon adopted for a variety of practical applications – such as teria. The evolution of bacteria – and therefore the emergence of dangerous
tracking outbreaks of the Zika and Ebola viruses. Furthermore, analyses by antibiotic resistance – can be studied following the same principles. However,
the Nextstrain team are incorporated into the yearly recommendation for the the challenge is somewhat greater for bacteria: their genome is much larger
makeup of the influenza vaccine and Neher has been an advisor to the WHO than that of viruses, and they do not only evolve by mutations, but also by ex-
Vaccine Composition Meetings since 2016. “This is a great example of how changing genes among each other. “It’s all a bit more complicated, but that’s
short the route from basic research to practical application can be.” exactly what fascinates me right now.”Research ––– 32 Research ––– 33
Professor Arber, Professor Kempf,
neurobiology has a reputation as
an incredibly complex research
field in which progress is only
made in tiny steps. What made
you choose it despite all this?
Arber –– Not despite, but precisely Arber –– We want to identify the
for these reasons. I never wanted networks that control the hundreds
to work in a field where all that re- of movement patterns our body
mained to be done was fill gaps. The performs. Just recently, we dis-
wonderful thing about neurobiology covered that there are groups of
“The greatest
is the opportunity to do things that neurons in the brainstem of mice
no one has ever done before. If I can that are responsible for very specific
Interview:
Yvonne Vahlensieck contribute a small amount of knowl- movements, such as reaching for
edge about how the brain works an apple. Now we want to know
challenge remains
that’s very satisfying for me. how this is controlled by the brain’s
Kempf –– I was originally motivated higher order centers. Thanks to – Prof. Anissa Kempf
to do neuroscience for philosophical new technologies, we are currently
reasons. For instance, I used to progressing in huge leaps. However,
the human brain”
wonder where consciousness was the greatest challenge in neurobiol-
located in the brain. But I quickly ogy remains the human brain, which
realized that this approach wasn’t continues to elude current methods.
going to get me anywhere. What
fascinates me now is how neural That’s why you’re both working
networks have the capacity to en- with animal models. Are your
code so many different complex pat- findings nevertheless transferrable
terns of behavior. It is also precisely to humans, for example in the
the fact that we understand so little treatment of diseases?
that makes it interesting. Arber –– Absolutely, for example
for Parkinson’s disease. One of the
Can you briefly explain what most important findings of recent
you are trying to learn about the years is that it is not enough to acti-
brain? vate a particular region of the brain;
Kempf –– I am interested in why you have to target precisely the right – Prof. Silvia Arber
we feel tired and want to sleep. We neuronal populations.
know that there are cells in the brain Kempf –– Yes. Many psychological
Professor Silvia Arber has been that induce sleep when activated. problems, neurological and psychi-
conducting research at the Bio- Yet, we understand very little about atric disorders including depression
the physiological processes that
zentrum for more than twenty lead to their activation. That is what
are associated with sleep distress.
Certain sleep disorders can be an
years, while Professor Anissa we aim to find out. Right now, I am early sign of Parkinson’s, for example.
doing experiments in fruit flies. But
Kempf is a recent arrival. The two my next step would be to look at
Yet, we understand very little about
the reasons behind their co-existence.
neurobiologists explain what their whether the same principles also If I study sleep in fruit flies, some of
apply to mice.
research is about and discuss the concepts and molecular targets
are likely to be applicable to humans
collaboration at the Biozentrum. too, as many of the genes that play
an important role in these diseases
and in sleep are conserved.Research ––– 34 Research ––– 35
Professor Arber, can Professor Professor Kempf, you spent a
Kempf count on support in Basel number of years doing research
if she decides to perform her ex- in the UK. What did you take
periments on mice in the future? away from that experience?
Arber –– I am sure that Anissa will Kempf –– I learned to assert myself
have no problems at all to find help. in a highly competitive environment.
Neurons in the brain stem (green) communicate
In Basel, a synergistic environment Cutting-edge research is being done with the spinal cord to relay commands that
has emerged over the years in the in the UK under conditions that would trigger the body’s movements. Viruses that jump
across synaptic connections were used to reveal
form of the Neuroscience Network be unimaginable in Switzerland.
the distribution of these neurons between the
Basel, which is stronger than the Professor Arber, do you remember Working there made me realize how motor neurons in the brain stem (purple).
sum of its parts and has a strong the beginning of your time head- fantastic the research conditions
international reputation, as well. ing a research group? are here at the Biozentrum and how
Kempf –– I am delighted to be part Arber –– Yes, of course. Anissa is spoiled we are here in Switzerland in
of the Neuroscience Network Basel. right. The first team members are general.
On top of that, the unique combi- crucial, as they set the tone for Arber –– Absolutely. Many of the
nation of different disciplines at the the entire lab. I started out with a doctoral researchers I supervise only
Biozentrum provides the perfect highly capable lab technician who really learn to appreciate this when
environment for me since my work still works for me today. Professor they go abroad, and tell me how
is multidisciplinary in nature. Walter Gehring was very helpful great it was to work in Switzerland.
with the recruiting process at the
Professor Kempf, right now you’re time, as I was still in the US. It is
putting your first ever research really important to have people with
group together here at the Biozen- experience around you who will give
trum. How are you going about it? you their honest opinion, even if it’s
Kempf –– At first, I would like to not always easy to hear. I have also Movements are the result of intricate interac-
spend a lot of time in the lab to as- offered Anissa my support. tions between the nervous system and muscles.
Different areas of the brain stem control the vari-
semble many of the technical setups
ous movements of our arms and legs, such as
myself – if we can’t do the experi- Does it make any difference to you reaching for an object with one hand, via highly
ments, we can’t make progress in whether you mentor a woman or specialized connections in the spinal cord.
our projects. That’s why I’m starting a man?
with a lab technician with experience Arber –– No, I’ll support anyone
in molecular biology and a doctoral as long as they are talented. That’s
researcher who has worked with what I have always done.
fruit flies before. Kempf –– No, I myself would like
to be valued primarily for my work
rather than my gender, but it is
crucial that women and men receive
the same opportunities. There is still
a lot of work to be done along those
lines and I sincerely hope that this
will continue to change in the future.
Our brain is a network comprising some 200
billion neurons. These neurons feature numerous
projections that connect them and enable them
to communicate with each other.Research ––– 36 Research ––– 37
Research under real-life
conditions
New approaches
“Until now, all antibiotics have suffer from chronic infections of
essentially been discovered using their lungs with the bacterium
the same approach,” says Christoph Pseudomonas aeruginosa. “We want
Dehio – specifically, by means of to understand how, over several
in the fight
tests performed on bacteria grown decades, bacteria develop the ability
in the lab under optimal conditions. to survive treatment with antibiotics
Text:
Yvonne Vahlensieck Conditions inside the human body virtually unscathed.”
are quite different, however. “This
against bacteria
“Over time, our work has increas- is why we want to gain a better un-
ingly been defined by a shared derstanding of pathogens during the
interest in antibiotics research,” says actual infection in patients.” Once
Professor Christoph Dehio, a group researchers can reproduce these
leader at the Biozentrum since the processes in the laboratory, the
year 2000. This trend is explained plan is for engineers to develop test
by an alarming surge in bacteria that systems mimicking patient tissue to
no longer respond well – if at all – screen for new active substances.
to treatment with antibiotics. The
WHO estimates that antibiotic-re- As an example of this approach,
sistant pathogens are responsible Christoph Dehio cites his own
Infection biology at the Biozen- for 700,000 deaths each year. These research on Escherichia coli, a gut
trum is undergoing a paradigm pathogens also increase the risk bacterium that can cause acute
associated with routine operations and chronic bladder infections –
shift: By shedding light on the such as appendectomies. and in severe cases can trigger
interaction between pathogen- life-threatening blood poisoning.
“We’re not just interested in un- To understand the mechanisms be-
ic bacteria and their human derstanding the underlying mech- hind these infections, it is necessary
hosts under natural conditions, anisms – we want to find ways to to consider processes in the tissue
successfully treat these infections,” of the ureter, bladder and kidneys,
researchers hope to generate explains Christoph Dehio. Efforts to as well as the immune system.
novel ideas for treatment. this end resulted in the creation of
the National Center of Competence “Solving the problem as a whole
Research on bacteria and viruses has a long tradition at in Research (NCCR) “AntiResist”, requires a transdisciplinary approach,”
– Prof. Urs Jenal
the Biozentrum. From the beginning, group leaders such approved last year by the Swiss says Urs Jenal. “Such an approach
as Professor Eduard Kellenberger and Professor Werner National Science Foundation and led depends on close collaboration be-
Arber made use of these microorganisms to study fun- by Christoph Dehio, Urs Jenal and tween basic researchers, clinicians The two group leaders believe that
damental molecular biological processes. Their ground- Professor Dirk Bumann. Aside from and engineers. With the NCCR we in the medium term, the COVID-19
breaking findings can still be found in textbooks today. the Biozentrum, the NCCR includes now have a framework that makes pandemic will result in greater
The last members of this “founding generation” were research teams of the University this possible.” awareness of the threat posed by
just about to retire when Professor Urs Jenal joined the Hospital Basel and the ETH Depart- antibiotic resistance. “The problem
Biozentrum a little over 25 years ago. “Microbiology at ment of Biosystems Science and Jenal himself has a long-standing is not coming at us all that fast, but
– Prof. Christoph Dehio
the Biozentrum had to reinvent itself,” he recalls. The new Engineering (D-BSSE) at its primary collaboration with clinicians at it is growing steadily,” says Christoph
groups carved out their own approach, ultimately estab- location Basel, while additional University Hospital Basel to inves- Dehio. Urs Jenal agrees: “The situa-
lishing the Biozentrum at the forefront of Swiss infection research groups are based in Zurich, tigate samples from cystic fibrosis tion is going to get worse gradually,
biology research. Lausanne and Israel. patients. These patients generally like a clock ticking.”Research ––– 38 Research ––– 39
The Canadian-born researcher’s thirst for
knowledge runs in the family – her father
is an engineer and her mother a classics
teacher. She continued both traditions at
McGill University in Montreal, studying
biochemistry alongside philosophy and In 2014, she accepted a professorship
history of science. “This taught me to in molecular stem cell biology at the
A stem cell think about the bigger picture.” She
caught the stem cell bug over 20 years
ago during her doctoral thesis at The
Rockefeller University in New York – and
Biozentrum. What was it like to go
from a bustling mega-metropolis to the
relatively sedate city of Basel? Looking
back, it was just right: “I love New York,
researcher never recovered. At the time, she was
characterizing a group of neural stem
cells in mice located in a niche in the lat-
eral ventricle. These cells – the existence
but Basel is a great place to live.” Fiona
Doetsch rhapsodizes about the small but
vibrant cultural scene and idyllic walks
along the Rhine. What is more, her son’s
to the core of which had long been doubted –
have the remarkable ability to create
new brain cells over an entire life-
time. Fiona Doetsch theorized that this
school activities helped the family to
quickly form social ties.
The move paid off in professional terms
phenomenon was central to the plastic too: In 2018, Fiona Doetsch was awarded
nature of the brain, which has to con- an ERC Grant of almost 3 million Swiss
When Professor Fiona Doetsch stantly adjust to new circumstances. francs, and two years later she was
talks about her work with stem At the same time, it offered prospects elected a member of the European
for the treatment of brain diseases. Molecular Biology Organization (EMBO).
cells, her enthusiasm is contagious. Her work at the Biozentrum revolves
“My field draws on various different Fiona Doetsch therefore decided to stick around the question
disciplines, such as neurobiology with this topic: first as a junior fellow at of how different “I love New
the Harvard University Society, and then physiological states
and developmental biology,” she from 2003 as a professor at Columbia such as hunger or York, but Basel
explains. “I believe it is precisely at University in New York. Gradually, she exertion can selec- is a great place
discovered how the stem cells in her tively trigger the
these intersections that the most niche are controlled by complex interac- formation of certain to live.”
tions involving multiple factors, including neurons and sup-
exciting research takes place.” signals from other parts of the brain and porting cells. At the – Prof. Fiona Doetsch
Text: neurotransmitters such as endorphins. moment, her group
Yvonne Vahlensieck is eager to uncover the role of stem
cells and their progeny in pregnancy and
motherhood.
One thing is quite clear: Fiona Doetsch
still finds research into “her” stem cell
niche just as thrilling as on the very first
day. “Only recently, we discovered sev-
eral completely new types of supporting
cells. We still have no idea what they do.
There are so many fantastic surprises to
come!”Research ––– 40 Research ––– 41
The three long-standing Characteristic
50 years of themes of the last 50 years
protein
terms by decade
1971 – 1981
research at the
nerve growth factor
term mentioned in 5,897 bacteriophage
publications (58.3% of all
cell publications) structure membrane bilayer
enzyme
term mentioned in 5,120 term mentioned in 2,687 gel electrophoresis
Biozentrum
publications (50.6% of all publications (26.6% of all
publications) publications) 1982 – 1991
Data analysis: Simone Grumbacher / nuclear magnetic resonance (NMR)
Michael Podvinec gene
human liver microsomes
yeast mitochondria
For the past 50 years, researchers from the Biozentrum have membrane proteins
been publishing their results in a wide range of scientific journals. 1992 – 2001
open reading frame
An analysis of the terms used in the titles and abstracts of publica- polymerase chain reaction (PCR)
tions over the decades reveals developments, trends and even Research at all levels central nervous system
nuclear pore complex
atomic force microscope (AFM)
the occasional surprise…
(macro-)molecules nanometer
amino acid sequence, enzyme,
2002 – 2011
binding site, nuclear pore
Discovery of and (multi-)mole- 0.4 x 10-9 m to
transcription factors
120 x 10-9 m
complex, molecular dynamics
cular complexes
TOR
simulation binding sites
Number of Biozentrum endoplasmic reticulum
development
publications since 1971 single cells
micrometer
0.2 x 10-6 m to
organelles, cell growth and
division, cell death, cell types,
target of rapamycin (TOR)
50 x 10-6 m bacterial secretion systems 2012 – 2021
500
Since the discovery of TOR in 1991, (neural) stem cells
the term has been mentioned in a skeletal muscle
type VI secretion system
400 total of 453 publications from the
Alzheimer’s disease
Biozentrum.
molecular dynamics simulations
stem cell, development,
multicellular micrometer
to meter nervous system, biofilms,
300
systems 12 x 10-6 m to 1 m skeletal muscle
200
100
10,111
scientific publications were published
fundamental
biomedical
from the individual
organ to the whole
organism
cancer, neurodegeneration,
autism spectrum disorders,
congenital and age-related muscle
from the Biozentrum between October research loss, antibiotic resistance
1971 and February 2021.
1971 1981 1991 2001 2011 2020
1997
isothermal titration
1974 calorimetry
nuclear magnetic 1994 term mentioned 1.1%
atomic force microscopy of all publications
Techniques resonance spectroscopy 1990 Unexpected term
1972 (NMR) 1975 PCR
term mentioned
appearing and electron microscopy term mentioned in 4.8% circular dichroism in 2.6% of all publications
surface plasmon “unknown mechanism”
term mentioned resonance
used in the term mentioned in 5.3% of all publications term mentioned in in 2.4% of all confocal microscopy term mentioned 0.4% A hallmark of science is that new findings give rise to new
publications of all publications 1.9% of all publications publications term mentioned 4.8% of all publications questions. Scientists communicate new discoveries and
gel electrophoresis
of all publications highlight areas where knowledge is still lacking. With this in
term mentioned in 1.5%
green fluorescent mind, it’s hardly surprising that this term has appeared
of all publications
protein in 23 publications…
term mentioned 1.2%
These data are based on publications linked to the Biozentrum between 1971 and February 2021. The source databases were Scopus, Web of Science and PubMed, and of all publications
the term frequency was determined by searching for all combinations of one to three words in order to establish how many publications mention the terms in their title or
abstract. Bibliometric data were provided by Max Hintermann from the University Library Basel.Research ––– 43 State-of-the-art technology Cutting-edge research requires the very latest technologies and specific know-how. The technology platforms at the Biozentrum give scientists access to world-class instru- mentation and state-of-the-art technologies, besides supporting them with their services and expertise. Text: Katrin Bühler
Research ––– 44 Research ––– 45
BSL-3 Laboratory
The Biosafety Level 3 Laboratory Proteomics Core Facility
offers researchers a facility for study- Proteins are a major component
ing highly infectious bacteria and of all living organisms. Using mass
viruses that cause serious diseases spectrometry, researchers can an-
under the strictest safety conditions. alyze the entire set of proteins, the
The BSL-3 Laboratory staff train and NMR Facility proteome, expressed in an organism.
support researchers in their work Nuclear magnetic resonance (NMR) For this purpose, the Proteomics
with pathogens. The facility also spectroscopy is indispensable for Core Facility provides the latest
has an on-site cell sorter to perform the elucidation of biological struc- technology and support from A to Z,
experiments with isolated cells. tures and functions at the atomic including technical project design,
level. Using the powerful high-reso- sample preparation, optimization of
FACS Core Facility lution NMR spectrometers housed analytical methods, the actual analy-
Fluorescence-activated Cell Sorting at the NMR Facility, researchers can sis of samples, and the evaluation of Research IT
BioEM Lab (FACS) is a very powerful technology investigate the molecular structure the data obtained. In biological research, large datasets
Electron microscopy is one of the that allows researchers to rapidly and dynamics of macromolecules and their analysis are increasingly
most useful techniques for studying and accurately characterize single such as proteins or nucleic acids and Research Instrumenta- prevalent, often causing difficult
the structure of biological molecules. fluorescently labeled cells. Besides characterize their interactions. As tion Facility technical and organizational challen-
The BioEM Lab offers researchers analysis of cell mixtures and other part of the Swiss Ultrahighfield Solu- The Research Instrumentation Facility ges for research endeavors. At the
a wide range of techniques from single particles such as bacteria and tion NMR Facility consortium, the (RIF) combines scientific consulting intersection between biology and in-
transmission electron microscopy cell organelles, the FACS Core Facility Imaging Core Facility Biozentrum NMR Facility – together services with a rapid prototyping formation technology, the Research
(TEM) and electron tomography also enables the research groups to Light microscopy and image analysis with the University of Zurich and workshop. The RIF supports re- IT platform closely collaborates
for visualizing the fine structure of purify and isolate specific cells using are important tools in modern life ETH Zurich – operates a series of search groups with the selection of with the other platforms and central
cells to cryo-electron microscopy for the flow cytometers provided. sciences. A wide range of highly spectrometers ranging from medium suitable technologies and adoption infrastructure providers. It advises
determining the three-dimensional sophisticated light microscopes en- field strengths to an ultrahigh field of non-commercial solutions, in and supports researchers with regard
structure of biomolecules such as ables diverse insights into the cells of 1.2 GHz. These NMR instruments addition to developing instrument to the IT systems, tools and proces-
proteins. and tissues of organisms. The Imag- open up entirely new research pos- prototypes. The team maintains a ses needed for smooth and effective
ing Core Facility provides researchers sibilities. makerspace and assists researchers research, data management and
Biophysics Facility with technical support for imaging in project planning and coordination, analysis.
The Biophysics Facility supports procedures and data analysis. The matching their needs to the skills
researchers with the use of sophis- team’s tasks also include establishing of the technology platforms and Researchers at the Biozentrum can
ticated instrumentation to measure novel techniques and developing workshops. also use three other university-affilia-
the interactions, reactions, stability new applications. ted technology platforms: the Geno-
and size of biological molecules such mics Facility Basel, the Life Sciences
as proteins and nucleic acids. The Training Facility and the Center for
equipment at the facility includes Scientific Computing, sciCORE.
instruments for microcalorimetry,
fluorescence spectroscopy, ultra-
centrifugation and light-scattering
measurements.You can also read
