The 2017 Nobel Prizes Thread

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jwl
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The 2017 Nobel Prizes Thread

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The Medicine and Physics Nobels are out-

Physics:
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics 2017 with one half to

Rainer Weiss
LIGO/VIRGO Collaboration

and the other half jointly to

Barry C. Barish
LIGO/VIRGO Collaboration

and

Kip S. Thorne
LIGO/VIRGO Collaboration

"for decisive contributions to the LIGO detector and the observation of gravitational waves"

Gravitational waves finally captured
On 14 September 2015, the universe's gravitational waves were observed for the very first time. The waves, which were predicted by Albert Einstein a hundred years ago, came from a collision between two black holes. It took 1.3 billion years for the waves to arrive at the LIGO detector in the USA.

The signal was extremely weak when it reached Earth, but is already promising a revolution in astrophysics. Gravitational waves are an entirely new way of observing the most violent events in space and testing the limits of our knowledge.

LIGO, the Laser Interferometer Gravitational-Wave Observatory, is a collaborative project with over one thousand researchers from more than twenty countries. Together, they have realised a vision that is almost fifty years old. The 2017 Nobel Laureates have, with their enthusiasm and determination, each been invaluable to the success of LIGO. Pioneers Rainer Weiss and Kip S. Thorne, together with Barry C. Barish, the scientist and leader who brought the project to completion, ensured that four decades of effort led to gravitational waves finally being observed.

In the mid-1970s, Rainer Weiss had already analysed possible sources of background noise that would disturb measurements, and had also designed a detector, a laser-based interferometer, which would overcome this noise. Early on, both Kip Thorne and Rainer Weiss were firmly convinced that gravitational waves could be detected and bring about a revolution in our knowledge of the universe.

Gravitational waves spread at the speed of light, filling the universe, as Albert Einstein described in his general theory of relativity. They are always created when a mass accelerates, like when an ice-skater pirouettes or a pair of black holes rotate around each other. Einstein was convinced it would never be possible to measure them. The LIGO project's achievement was using a pair of gigantic laser interferometers to measure a change thousands of times smaller than an atomic nucleus, as the gravitational wave passed the Earth.

So far all sorts of electromagnetic radiation and particles, such as cosmic rays or neutrinos, have been used to explore the universe. However, gravitational waves are direct testimony to disruptions in spacetime itself. This is something completely new and different, opening up unseen worlds. A wealth of discoveries awaits those who succeed in capturing the waves and interpreting their message.
https://www.nobelprize.org/nobel_prizes ... press.html

Medicine:
Press Release
2017-10-02

The Nobel Assembly at Karolinska Institutet has today decided to award

the 2017 Nobel Prize in Physiology or Medicine

jointly to

Jeffrey C. Hall, Michael Rosbash and Michael W. Young

for their discoveries of molecular mechanisms controlling the circadian rhythm

Summary
Life on Earth is adapted to the rotation of our planet. For many years we have known that living organisms, including humans, have an internal, biological clock that helps them anticipate and adapt to the regular rhythm of the day. But how does this clock actually work? Jeffrey C. Hall, Michael Rosbash and Michael W. Young were able to peek inside our biological clock and elucidate its inner workings. Their discoveries explain how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth's revolutions.

Using fruit flies as a model organism, this year's Nobel laureates isolated a gene that controls the normal daily biological rhythm. They showed that this gene encodes a protein that accumulates in the cell during the night, and is then degraded during the day. Subsequently, they identified additional protein components of this machinery, exposing the mechanism governing the self-sustaining clockwork inside the cell. We now recognize that biological clocks function by the same principles in cells of other multicellular organisms, including humans.

With exquisite precision, our inner clock adapts our physiology to the dramatically different phases of the day. The clock regulates critical functions such as behavior, hormone levels, sleep, body temperature and metabolism. Our wellbeing is affected when there is a temporary mismatch between our external environment and this internal biological clock, for example when we travel across several time zones and experience "jet lag". There are also indications that chronic misalignment between our lifestyle and the rhythm dictated by our inner timekeeper is associated with increased risk for various diseases.

Our inner clock
Most living organisms anticipate and adapt to daily changes in the environment. During the 18th century, the astronomer Jean Jacques d'Ortous de Mairan studied mimosa plants, and found that the leaves opened towards the sun during daytime and closed at dusk. He wondered what would happen if the plant was placed in constant darkness. He found that independent of daily sunlight the leaves continued to follow their normal daily oscillation (Figure 1). Plants seemed to have their own biological clock.

Other researchers found that not only plants, but also animals and humans, have a biological clock that helps to prepare our physiology for the fluctuations of the day. This regular adaptation is referred to as the circadian rhythm, originating from the Latin words circa meaning "around" and dies meaning "day". But just how our internal circadian biological clock worked remained a mystery.

Mimosa plants in window

Figure 1. An internal biological clock. The leaves of the mimosa plant open towards the sun during day but close at dusk (upper part). Jean Jacques d'Ortous de Mairan placed the plant in constant darkness (lower part) and found that the leaves continue to follow their normal daily rhythm, even without any fluctuations in daily light.

Identification of a clock gene
During the 1970's, Seymour Benzer and his student Ronald Konopka asked whether it would be possible to identify genes that control the circadian rhythm in fruit flies. They demonstrated that mutations in an unknown gene disrupted the circadian clock of flies. They named this gene period. But how could this gene influence the circadian rhythm?

This year's Nobel Laureates, who were also studying fruit flies, aimed to discover how the clock actually works. In 1984, Jeffrey Hall and Michael Rosbash, working in close collaboration at Brandeis University in Boston, and Michael Young at the Rockefeller University in New York, succeeded in isolating the period gene. Jeffrey Hall and Michael Rosbash then went on to discover that PER, the protein encoded by period, accumulated during the night and was degraded during the day. Thus, PER protein levels oscillate over a 24-hour cycle, in synchrony with the circadian rhythm.

A self-regulating clockwork mechanism
The next key goal was to understand how such circadian oscillations could be generated and sustained. Jeffrey Hall and Michael Rosbash hypothesized that the PER protein blocked the activity of the period gene. They reasoned that by an inhibitory feedback loop, PER protein could prevent its own synthesis and thereby regulate its own level in a continuous, cyclic rhythm (Figure 2A).

Simplified illustration of the feedback regulation of the period gene
Figure 2A. A simplified illustration of the feedback regulation of the period gene. The figure shows the sequence of events during a 24h oscillation. When the period gene is active, period mRNA is made. The mRNA is transported to the cell's cytoplasm and serves as template for the production of PER protein. The PER protein accumulates in the cell's nucleus, where the period gene activity is blocked. This gives rise to the inhibitory feedback mechanism that underlies a circadian rhythm.

The model was tantalizing, but a few pieces of the puzzle were missing. To block the activity of the period gene, PER protein, which is produced in the cytoplasm, would have to reach the cell nucleus, where the genetic material is located. Jeffrey Hall and Michael Rosbash had shown that PER protein builds up in the nucleus during night, but how did it get there? In 1994 Michael Young discovered a second clock gene, timeless, encoding the TIM protein that was required for a normal circadian rhythm. In elegant work, he showed that when TIM bound to PER, the two proteins were able to enter the cell nucleus where they blocked period gene activity to close the inhibitory feedback loop (Figure 2B).

The molecular components of the circadian clock.
Figure 2B. A simplified illustration of the molecular components of the circadian clock.

Such a regulatory feedback mechanism explained how this oscillation of cellular protein levels emerged, but questions lingered. What controlled the frequency of the oscillations? Michael Young identified yet another gene, doubletime, encoding the DBT protein that delayed the accumulation of the PER protein. This provided insight into how an oscillation is adjusted to more closely match a 24-hour cycle.

The paradigm-shifting discoveries by the laureates established key mechanistic principles for the biological clock. During the following years other molecular components of the clockwork mechanism were elucidated, explaining its stability and function. For example, this year's laureates identified additional proteins required for the activation of the period gene, as well as for the mechanism by which light can synchronize the clock.

Keeping time on our human physiology
The biological clock is involved in many aspects of our complex physiology. We now know that all multicellular organisms, including humans, utilize a similar mechanism to control circadian rhythms. A large proportion of our genes are regulated by the biological clock and, consequently, a carefully calibrated circadian rhythm adapts our physiology to the different phases of the day (Figure 3). Since the seminal discoveries by the three laureates, circadian biology has developed into a vast and highly dynamic research field, with implications for our health and wellbeing.

The circadian clock
Figure 3. The circadian clock anticipates and adapts our physiology to the different phases of the day. Our biological clock helps to regulate sleep patterns, feeding behavior, hormone release, blood pressure, and body temperature.
https://www.nobelprize.org/nobel_prizes ... press.html
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jwl
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Re: The 2017 Nobel Prizes Thread

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The Chemistry prize is out:
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2017 to

Jacques Dubochet
University of Lausanne, Switzerland

Joachim Frank
Columbia University, New York, USA

and

Richard Henderson
MRC Laboratory of Molecular Biology, Cambridge, UK

"for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution"



Cool microscope technology revolutionises biochemistry
We may soon have detailed images of life’s complex machineries in atomic resolution. The Nobel Prize in Chemistry 2017 is awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for the development of cryo-electron microscopy, which both simplifies and improves the imaging of biomolecules. This method has moved biochemistry into a new era.

A picture is a key to understanding. Scientific breakthroughs often build upon the successful visualisation of objects invisible to the human eye. However, biochemical maps have long been filled with blank spaces because the available technology has had difficulty generating images of much of life’s molecular machinery. Cryo-electron microscopy changes all of this. Researchers can now freeze biomolecules mid-movement and visualise processes they have never previously seen, which is decisive for both the basic understanding of life’s chemistry and for the development of pharmaceuticals.

Electron microscopes were long believed to only be suitable for imaging dead matter, because the powerful electron beam destroys biological material. But in 1990, Richard Henderson succeeded in using an electron microscope to generate a three-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential.

Joachim Frank made the technology generally applicable. Between 1975 and 1986 he developed an image processing method in which the electron microscope’s fuzzy twodimensional images are analysed and merged to reveal a sharp three-dimensional structure.

Jacques Dubochet added water to electron microscopy. Liquid water evaporates in the electron microscope’s vacuum, which makes the biomolecules collapse. In the early 1980s, Dubochet succeeded in vitrifying water – he cooled water so rapidly that it solidified in its liquid form around a biological sample, allowing the biomolecules to retain their natural shape even in a vacuum.

Following these discoveries, the electron microscope’s every nut and bolt have been optimised. The desired atomic resolution was reached in 2013, and researchers can now routinely produce three-dimensional structures of biomolecules. In the past few years, scientific literature has been filled with images of everything from proteins that cause antibiotic resistance, to the surface of the Zika virus. Biochemistry is now facing an explosive development and is all set for an exciting future.
https://www.nobelprize.org/nobel_prizes ... press.html
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Re: The 2017 Nobel Prizes Thread

Post by jwl »

Literature:
Kazuo Ishiguro
The Nobel Prize in Literature for 2017 is awarded to the English author Kazuo Ishiguro

"who, in novels of great emotional force, has uncovered the abyss beneath our illusory sense of connection with the world".
https://www.nobelprize.org/nobel_prizes ... press.html
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