6 ms·

The Nobel Prize in Chemistry 2014

78 points by srikar 12y ago

leoc 12y ago
Pics or it didn't happen.
sveme 12y ago
I remember one of the first papers coming out from Hell's group using STED microscopy, showing extremely fine-grained cytoskeleton structure and dynamics - I was in awe at the beauty and complexity of the resolved structures, similar to my reaction to images of the first GFP-tagged cytoskeleton proteins. These technologies create an intuitive understanding (though we obviously knew it before) that cells and all living things are self-organized reaction-diffusion systems - which should lead to a paradigm shift in thinking about biology, though that hasn't really happened yet. Sidenote: it's interesting that so many Nobel Prizes in Chemistry in the last decade or so went to quintessential biological discoveries (same with Medicine). Alfred Nobel should have included a prize for biology as well, I guess. Though in the end, borders between disciplines are fluid anyway.
- mrfusion 12y ago
  > cells and all living things are self-organized reaction-diffusion systems Sounds intriguing. Can you explain more what you mean?
  - craigyk 12y ago
    I'm going to guess he means they work via chemistry and exploiting heat in the system ie brownian ratchets.
    - Balgair 12y ago
      Specifically, Gibbs Free Energy (G = Heat - Temp*(Change in Entropy)). Basically, the energy available is the heat in the system minus some chaotic stuff (and no, you can't make it better, because physics). I have a good physics background and what is most supprising to me is how alive cells are. I initially came into the bio field just as the OP talks about, with the idea that cells are just tiny chemistry machines that are very complicated. I figured that eventually, we'd understand the cell from top to bottom give or take a century. Now.... not so much. Cells, especially eukaryotes like us and yeast, are just so alive to me. They do weird things and act on their own. You would think that with enough constraints in the inputs you would be able to very precisely predict what any one cell would do. Nope. They go off and do their own thing, replicate in some strange way, find some food source you never thought they could digest, eat each other, have sex in some novel way. And it's not just that you are not constraining the system enough either, or that the system is inherently chaotic and you see improbable events because of that. They really are alive and want to stay that way. I know this is not a good explanation, and that real science still has a lot to say about it. But with my background I felt the way OP did, that it was all overlapping Gaussian curves and gradients in N-space that makes it look alive. But now, having seen it up close and watched it all, now I am pretty certain that life is different somehow.
      - deleted 12y ago
        [deleted]
  - sveme 12y ago
    It's quite a vast topic. When you look at typical biochemistry text books, everything seems static. Even when something changes (e.g., some changes in the environment), some proteins are switched off, others switched on and the cell returns to a certain seemingly static state. What's missing in this picture are the incredible dynamics in the system. It is a truly complex dynamical system, constantly switching from one fix point to another. The rates of processes and the dynamic location of molecules plays a much more important role in the inner workings of a cell than was previously believed. To be more specific: Self Organization Cells and organisms have incredibly detailed structures or spatial and temporal patterns on time and space scales far beyond typical biochemical reaction rates and the sizes of the molecules. These patterns are not created by someone or something; they emerge from the localized dynamic interplay between many same and different molecules - self organization. In a certain sense the cell and any organism is a dynamical system that self-organizes into intricate patterns, something that is mostly only appreciated by physicists working in biology, rarely by biologists themselves. This has consequences that are often still not appreciated. An example (hope I recall it all correctly, it's been a few years): I was working on so-called Src-family protein kinases (SFKs), proteins that phosphorylate other proteins and thereby change their conformation so that they themselves become activated. SFKs play a huge role in many different signal transduction pathways and therefore in many different diseases. Because of their importancy they are regulated/controlled on many different levels. One of them is that they are self-inhibiting: they bind intramolecularly to a phosphate group and thereby block its own activity. To become activated, they need to be dephosphorylated by some phosphatase and they need to be phosphorylated at another position by another SFK intermolecularly. In the standard biological treatment, it's all pretty simple: phosphatase dephosphorylates, SFK phosphorylates - done. However, as SFKs bind themselves, they block access to the site that the phosphatase wants to dephosphorylate - why could this system then be responsive to any changes, why doesn't it simply stay in this state forever? Dynamics. SFKs most likely (that was more my hypothesis at that time, don't know what the situation is like now) constantly unbind and bind its inhibiting phosphate at a low rate. In its unbound state, the phosphatase can access the phosphate. As the active SFK in turn activates its own phosphatase (a feedback loop), more phosphatases are around, dephosphorylating more SFKs in their unbound conformation, leading to a mostly active population of SFKs. Now when you incorporate spatial aspects into this, you get yet another picture: as SFKs activate themselves constantly (via autophosphorylation), a simple accumulation of many SFKs in a certain part of the cell (e.g., the cell membrane) could be enough to move the whole system above an activation threshold, leading to a complete cell-wide SFK activation. This would not require any of the standard causes used to explain activations in biology. Hope I managed to get at least a little bit across of what I mean. In a nutshell: for me, the Nobel Prize was awarded today to a novel experimental method that nicely shows that cells are no bag full of chemicals and should not be investigated and explained as such; the role of spatial and temporal patterns is much underappreciated still. Or something like that.
- Osmium 12y ago
  > I remember one of the first papers coming out from Hell's group using STED microscopy, showing extremely fine-grained cytoskeleton structure and dynamics Do you have any links to this, or other seminal papers in the field? Alternatively, a gallery of images or even an art book appropriate for the layperson? I found this image on the wiki page comparing STED and confocal microscopy particularly striking and would love to see more like it: https://en.wikipedia.org/wiki/File:2color-STED-example.png https://en.wikipedia.org/wiki/File:2color-STED-example.png
  - toufka 12y ago
    Here's a pretty nice simulation/explanation of what makes STED work [1]. There are similar competing technologies that do essentially the same thing in order to arrive at sub-difraction-limited images including STORM & Structured Illumination. Google around for STORM, STED and the prettiest pictures will come from 'cytoskeletal' features, though some really interesting nano-mater-scale studies have been conducted with respect to synapses, the nuclear pore, and a number of other sub-cellular structures that would have otherwise been extraordinarily difficult. [1] http://microscopyu.com/tutorials/flash/superresolution/stedvsstorm/index.html http://microscopyu.com/tutorials/flash/superresolution/stedv...
    - Osmium 12y ago
      >There are similar competing technologies that do essentially the same thing in order to arrive at sub-difraction-limited images including STORM & Structured Illumination. Thanks for the info. Your mention of STORM led me to this: http://en.wikipedia.org/wiki/Super-resolution_microscopy http://en.wikipedia.org/wiki/Super-resolution_microscopy Given all these competing technologies, could you comment on why the Nobel was given to STED/PALM/STORM(?) in particular?
      - toufka 12y ago
        Primarily because they were 'first'. Part of the Nobel was awarded to Betzig & Moerner who helped make single particles identifiable. They developed some of the chemistries and molecules to make the microscopy possible. Hell did a bit more hard microscopy - he made the scopes, and took the photos using those single-particle techniques. I've never actually used STED, (PALM & STORM are the same, simultaneously co-invented). I have used STORM, and I think the reason is because they're technically a bit more straightforward and require some nice software on a standard scope rather than a bit more complicated scope. So STED, while a bit older, I think might be a bit harder to do technically than the newer (computational) techniques. All of them are super cool and in the past 5 years are quickly becoming 'standard techniques' that really will change the way people think about the structure of cells. They've increased our ability to peer into live, unperturbed cells from a resolution of ~200nm to as few as ~10nm - or the difference from being able to see that there is protein structure, to seeing what the structure is.
gilgoomesh 12y ago
The two techniques being awarded are: http://en.wikipedia.org/wiki/STED_microscopy http://en.wikipedia.org/wiki/STED_microscopy (Stefan Hell) and http://en.wikipedia.org/wiki/Photoactivated_localization_microscopy http://en.wikipedia.org/wiki/Photoactivated_localization_mic... (Eric Betzig and William Moerner)
mrfusion 12y ago
Could this be useful for CPU lithography? Anyone know?
- uaygsfdbzf 12y ago
  High resolution microscopy techniques rely on the fact that the fluorophores respond non-linearly to the excitation light. In the semiconductor industry a non-linear response in the photoresist was used (for 193nm) to obtain feature sizes considerably smaller than illumination wavelength and numerical aperture of the objective would suggest.
- gilgoomesh 12y ago
  I doubt it. It requires molecules that can selectively bind with fluorescent markers. I don't think you're going to get any interesting bindings just from doped silicon.
- troymc 12y ago
  Maybe. The two-laser setup of STED microscopy has similarities to this recently-developed technique: http://www.sciencealert.com.au/news/20140309-26116.html http://www.sciencealert.com.au/news/20140309-26116.html
DocSavage 12y ago
One of the prize winners, Eric Betzig, is the first Nobelist at the relatively new Janelia Research Center (http://janelia.org http://janelia.org). He has an interesting backstory, having taken a decade long detour from science. Betzig says, "there was this big gap on my résumé. So I knew I had to come up with some intellectual capital to get people to listen to me again." http://www.hhmi.org/news/eric-betzig-wins-2014-nobel-prize-chemistry http://www.hhmi.org/news/eric-betzig-wins-2014-nobel-prize-c... An interesting video: http://www.ibiology.org/ibiomagazine/issue-2/eric-betzig-and-harald-hess-developing-palm-microscopy.html http://www.ibiology.org/ibiomagazine/issue-2/eric-betzig-and... Here's the original paper describing PALM: http://janelia.org/sites/default/files/biblio/field_related_file/Betzig%20PALM%20Science%202006.pdf http://janelia.org/sites/default/files/biblio/field_related_...
- mikeyouse 12y ago
  A scientist / photographer I follow on Twitter (Bryan William Jones - @BWJones) took some pretty terrific shots of Janelia last spring, it's an amazing facility: http://prometheus.med.utah.edu/~bwjones/2014/04/janelia-farm/ http://prometheus.med.utah.edu/~bwjones/2014/04/janelia-farm... And the on-campus 'housing': http://prometheus.med.utah.edu/~bwjones/2014/03/room-at-janelia-farms/ http://prometheus.med.utah.edu/~bwjones/2014/03/room-at-jane...
  - DocSavage 12y ago
    The room in the picture is one of the short-term rooms used almost exclusively for visitors and conference attendees. Long-term on-campus townhouses and condos have nice modern designs but not that kind of view :)
jamesash 12y ago
Paul Bracher of ChemBark gave this field the highest odds of winning, at 7-1. Interestingly a commenter told him he neglected to put in Hell, about 3 hours before the announcement was made. http://blog.chembark.com/2014/10/08/predictions-for-the-2014-nobel-prize-in-chemistry/ http://blog.chembark.com/2014/10/08/predictions-for-the-2014... Compare to Thomson Reuters' predictions. http://thomsonreuters.com/press-releases/092014/2014-nobel-laureates-predictions http://thomsonreuters.com/press-releases/092014/2014-nobel-l...
cing 12y ago
I thought this was interesting: "Both Betzig and Moerner made their original pioneering discoveries in industry - Moerner when he was working at IBM in San Jose and Betzig when he was working in his own private company" - http://wavefunction.fieldofscience.com/2014/10/the-2014-nobel-prize-in-chemistry-and.html http://wavefunction.fieldofscience.com/2014/10/the-2014-nobe...
coldcode 12y ago
This is one reason I wish I had continued in PhD studies in Chemistry, to do stuff like this. Instead I became a programmer and now read HN.
dlau 12y ago
I'm super glad that Professor Moerner is getting credit where credit is due. Having taken his intro seminar and interned in his lab my freshmen year, I can attest he's a really great teacher as well. On a side note, I hope this added recognition will pump more money into his lab's equipment. Despite being a physical chemistry lab, their computers were painfully slow and outdated.

78 points by srikar 12y ago

leoc 12y ago

Pics or it didn't happen.

sveme 12y ago

I remember one of the first papers coming out from Hell's group using STED microscopy, showing extremely fine-grained cytoskeleton structure and dynamics - I was in awe at the beauty and complexity of the resolved structures, similar to my reaction to images of the first GFP-tagged cytoskeleton proteins. These technologies create an intuitive understanding (though we obviously knew it before) that cells and all living things are self-organized reaction-diffusion systems - which should lead to a paradigm shift in thinking about biology, though that hasn't really happened yet. Sidenote: it's interesting that so many Nobel Prizes in Chemistry in the last decade or so went to quintessential biological discoveries (same with Medicine). Alfred Nobel should have included a prize for biology as well, I guess. Though in the end, borders between disciplines are fluid anyway.

mrfusion 12y ago
> cells and all living things are self-organized reaction-diffusion systems Sounds intriguing. Can you explain more what you mean?
- craigyk 12y ago
  I'm going to guess he means they work via chemistry and exploiting heat in the system ie brownian ratchets.
  - Balgair 12y ago
    Specifically, Gibbs Free Energy (G = Heat - Temp*(Change in Entropy)). Basically, the energy available is the heat in the system minus some chaotic stuff (and no, you can't make it better, because physics). I have a good physics background and what is most supprising to me is how alive cells are. I initially came into the bio field just as the OP talks about, with the idea that cells are just tiny chemistry machines that are very complicated. I figured that eventually, we'd understand the cell from top to bottom give or take a century. Now.... not so much. Cells, especially eukaryotes like us and yeast, are just so alive to me. They do weird things and act on their own. You would think that with enough constraints in the inputs you would be able to very precisely predict what any one cell would do. Nope. They go off and do their own thing, replicate in some strange way, find some food source you never thought they could digest, eat each other, have sex in some novel way. And it's not just that you are not constraining the system enough either, or that the system is inherently chaotic and you see improbable events because of that. They really are alive and want to stay that way. I know this is not a good explanation, and that real science still has a lot to say about it. But with my background I felt the way OP did, that it was all overlapping Gaussian curves and gradients in N-space that makes it look alive. But now, having seen it up close and watched it all, now I am pretty certain that life is different somehow.
    - deleted 12y ago
      [deleted]
- sveme 12y ago
  It's quite a vast topic. When you look at typical biochemistry text books, everything seems static. Even when something changes (e.g., some changes in the environment), some proteins are switched off, others switched on and the cell returns to a certain seemingly static state. What's missing in this picture are the incredible dynamics in the system. It is a truly complex dynamical system, constantly switching from one fix point to another. The rates of processes and the dynamic location of molecules plays a much more important role in the inner workings of a cell than was previously believed. To be more specific: Self Organization Cells and organisms have incredibly detailed structures or spatial and temporal patterns on time and space scales far beyond typical biochemical reaction rates and the sizes of the molecules. These patterns are not created by someone or something; they emerge from the localized dynamic interplay between many same and different molecules - self organization. In a certain sense the cell and any organism is a dynamical system that self-organizes into intricate patterns, something that is mostly only appreciated by physicists working in biology, rarely by biologists themselves. This has consequences that are often still not appreciated. An example (hope I recall it all correctly, it's been a few years): I was working on so-called Src-family protein kinases (SFKs), proteins that phosphorylate other proteins and thereby change their conformation so that they themselves become activated. SFKs play a huge role in many different signal transduction pathways and therefore in many different diseases. Because of their importancy they are regulated/controlled on many different levels. One of them is that they are self-inhibiting: they bind intramolecularly to a phosphate group and thereby block its own activity. To become activated, they need to be dephosphorylated by some phosphatase and they need to be phosphorylated at another position by another SFK intermolecularly. In the standard biological treatment, it's all pretty simple: phosphatase dephosphorylates, SFK phosphorylates - done. However, as SFKs bind themselves, they block access to the site that the phosphatase wants to dephosphorylate - why could this system then be responsive to any changes, why doesn't it simply stay in this state forever? Dynamics. SFKs most likely (that was more my hypothesis at that time, don't know what the situation is like now) constantly unbind and bind its inhibiting phosphate at a low rate. In its unbound state, the phosphatase can access the phosphate. As the active SFK in turn activates its own phosphatase (a feedback loop), more phosphatases are around, dephosphorylating more SFKs in their unbound conformation, leading to a mostly active population of SFKs. Now when you incorporate spatial aspects into this, you get yet another picture: as SFKs activate themselves constantly (via autophosphorylation), a simple accumulation of many SFKs in a certain part of the cell (e.g., the cell membrane) could be enough to move the whole system above an activation threshold, leading to a complete cell-wide SFK activation. This would not require any of the standard causes used to explain activations in biology. Hope I managed to get at least a little bit across of what I mean. In a nutshell: for me, the Nobel Prize was awarded today to a novel experimental method that nicely shows that cells are no bag full of chemicals and should not be investigated and explained as such; the role of spatial and temporal patterns is much underappreciated still. Or something like that.
Osmium 12y ago
> I remember one of the first papers coming out from Hell's group using STED microscopy, showing extremely fine-grained cytoskeleton structure and dynamics Do you have any links to this, or other seminal papers in the field? Alternatively, a gallery of images or even an art book appropriate for the layperson? I found this image on the wiki page comparing STED and confocal microscopy particularly striking and would love to see more like it: https://en.wikipedia.org/wiki/File:2color-STED-example.png https://en.wikipedia.org/wiki/File:2color-STED-example.png
- toufka 12y ago
  Here's a pretty nice simulation/explanation of what makes STED work [1]. There are similar competing technologies that do essentially the same thing in order to arrive at sub-difraction-limited images including STORM & Structured Illumination. Google around for STORM, STED and the prettiest pictures will come from 'cytoskeletal' features, though some really interesting nano-mater-scale studies have been conducted with respect to synapses, the nuclear pore, and a number of other sub-cellular structures that would have otherwise been extraordinarily difficult. [1] http://microscopyu.com/tutorials/flash/superresolution/stedvsstorm/index.html http://microscopyu.com/tutorials/flash/superresolution/stedv...
  - Osmium 12y ago
    >There are similar competing technologies that do essentially the same thing in order to arrive at sub-difraction-limited images including STORM & Structured Illumination. Thanks for the info. Your mention of STORM led me to this: http://en.wikipedia.org/wiki/Super-resolution_microscopy http://en.wikipedia.org/wiki/Super-resolution_microscopy Given all these competing technologies, could you comment on why the Nobel was given to STED/PALM/STORM(?) in particular?
    - toufka 12y ago
      Primarily because they were 'first'. Part of the Nobel was awarded to Betzig & Moerner who helped make single particles identifiable. They developed some of the chemistries and molecules to make the microscopy possible. Hell did a bit more hard microscopy - he made the scopes, and took the photos using those single-particle techniques. I've never actually used STED, (PALM & STORM are the same, simultaneously co-invented). I have used STORM, and I think the reason is because they're technically a bit more straightforward and require some nice software on a standard scope rather than a bit more complicated scope. So STED, while a bit older, I think might be a bit harder to do technically than the newer (computational) techniques. All of them are super cool and in the past 5 years are quickly becoming 'standard techniques' that really will change the way people think about the structure of cells. They've increased our ability to peer into live, unperturbed cells from a resolution of ~200nm to as few as ~10nm - or the difference from being able to see that there is protein structure, to seeing what the structure is.

gilgoomesh 12y ago

The two techniques being awarded are: http://en.wikipedia.org/wiki/STED_microscopy http://en.wikipedia.org/wiki/STED_microscopy (Stefan Hell) and http://en.wikipedia.org/wiki/Photoactivated_localization_microscopy http://en.wikipedia.org/wiki/Photoactivated_localization_mic... (Eric Betzig and William Moerner)

mrfusion 12y ago

Could this be useful for CPU lithography? Anyone know?

uaygsfdbzf 12y ago
High resolution microscopy techniques rely on the fact that the fluorophores respond non-linearly to the excitation light. In the semiconductor industry a non-linear response in the photoresist was used (for 193nm) to obtain feature sizes considerably smaller than illumination wavelength and numerical aperture of the objective would suggest.
gilgoomesh 12y ago
I doubt it. It requires molecules that can selectively bind with fluorescent markers. I don't think you're going to get any interesting bindings just from doped silicon.
troymc 12y ago
Maybe. The two-laser setup of STED microscopy has similarities to this recently-developed technique: http://www.sciencealert.com.au/news/20140309-26116.html http://www.sciencealert.com.au/news/20140309-26116.html

DocSavage 12y ago

One of the prize winners, Eric Betzig, is the first Nobelist at the relatively new Janelia Research Center (http://janelia.org http://janelia.org). He has an interesting backstory, having taken a decade long detour from science. Betzig says, "there was this big gap on my résumé. So I knew I had to come up with some intellectual capital to get people to listen to me again." http://www.hhmi.org/news/eric-betzig-wins-2014-nobel-prize-chemistry http://www.hhmi.org/news/eric-betzig-wins-2014-nobel-prize-c... An interesting video: http://www.ibiology.org/ibiomagazine/issue-2/eric-betzig-and-harald-hess-developing-palm-microscopy.html http://www.ibiology.org/ibiomagazine/issue-2/eric-betzig-and... Here's the original paper describing PALM: http://janelia.org/sites/default/files/biblio/field_related_file/Betzig%20PALM%20Science%202006.pdf http://janelia.org/sites/default/files/biblio/field_related_...

mikeyouse 12y ago
A scientist / photographer I follow on Twitter (Bryan William Jones - @BWJones) took some pretty terrific shots of Janelia last spring, it's an amazing facility: http://prometheus.med.utah.edu/~bwjones/2014/04/janelia-farm/ http://prometheus.med.utah.edu/~bwjones/2014/04/janelia-farm... And the on-campus 'housing': http://prometheus.med.utah.edu/~bwjones/2014/03/room-at-janelia-farms/ http://prometheus.med.utah.edu/~bwjones/2014/03/room-at-jane...
- DocSavage 12y ago
  The room in the picture is one of the short-term rooms used almost exclusively for visitors and conference attendees. Long-term on-campus townhouses and condos have nice modern designs but not that kind of view :)

jamesash 12y ago

Paul Bracher of ChemBark gave this field the highest odds of winning, at 7-1. Interestingly a commenter told him he neglected to put in Hell, about 3 hours before the announcement was made. http://blog.chembark.com/2014/10/08/predictions-for-the-2014-nobel-prize-in-chemistry/ http://blog.chembark.com/2014/10/08/predictions-for-the-2014... Compare to Thomson Reuters' predictions. http://thomsonreuters.com/press-releases/092014/2014-nobel-laureates-predictions http://thomsonreuters.com/press-releases/092014/2014-nobel-l...

cing 12y ago

I thought this was interesting: "Both Betzig and Moerner made their original pioneering discoveries in industry - Moerner when he was working at IBM in San Jose and Betzig when he was working in his own private company" - http://wavefunction.fieldofscience.com/2014/10/the-2014-nobel-prize-in-chemistry-and.html http://wavefunction.fieldofscience.com/2014/10/the-2014-nobe...

coldcode 12y ago

This is one reason I wish I had continued in PhD studies in Chemistry, to do stuff like this. Instead I became a programmer and now read HN.

dlau 12y ago

I'm super glad that Professor Moerner is getting credit where credit is due. Having taken his intro seminar and interned in his lab my freshmen year, I can attest he's a really great teacher as well. On a side note, I hope this added recognition will pump more money into his lab's equipment. Despite being a physical chemistry lab, their computers were painfully slow and outdated.