Nobel Prize in Chemistry 2017: Cryo-electron microscopy(Part ll )
आखिर क्रायो -इलेक्ट्रॉन माइक्रोस्कोपी की जरूरत क्या है ?क्यों है ?
क्या दिक्कतें पेश आती रहीं हैं ट्रांसमिशन इलक्ट्रोन माइक्रोस्कोप एवं
क्रिस्टलोग्रेफी में -क्यों महत्वपूर्ण हो उठी कूल माक्रोस्कोपी ?
क्या दिक्कतें पेश आती रहीं हैं ट्रांसमिशन इलक्ट्रोन माइक्रोस्कोप एवं
क्रिस्टलोग्रेफी में -क्यों महत्वपूर्ण हो उठी कूल माक्रोस्कोपी ?
बेशक विशेष किस्म के यौगिक एवं अन्य सूक्ष्मदर्शी उन संरचनाओं का खुलासा करते आये हैं जो न तो नंगी आँखों देखे जा सकीं और न साधरण सूक्ष्मदर्शी ही विशेष मददगार सिद्ध हुए। क्योंकि इनकी विभेदन क्षमता ( दो आणविक /परमाणुविक संरचनाओं को साफ़ -साफ़ और अलग दिखलाना )प्रकाश की तरंग -लम्बाई से सीमित हो जाती है। वहां तो ये बिलकुल किसी काम नहीं आते जहां संरचनाएं और भी छोटी होती जातीं हैं तकरीबन परमाणुविक आकार से टक्कर लेती हुई रहतीं हैं।
अब इलेक्ट्रॉन सूक्ष्मदर्शी काम आता है लेकिन गैर -जैविक अणुओं की पड़ताल तक ही यह कारगर सिद्ध होता है जैविक अणुओं को इसमें प्रयुक्त इलेक्ट्रॉन पुंज भस्म कर डालता है। विकल्प के तौर पर विज्ञानी एक्स -रे -क्रिस्टलो -ग्रेफी (X-ray crystallography ) आज़माते हैं जिसके लिए ज़रूरी रहता है उस आणविक साम्पिल में अणु एक ख़ास क्रम में न सिर्फ व्यवस्थित होवें वही क्रम अपने को पूरी संरचना में दोहराता दिखे।
अब जरूरी नहीं है सभी अन्वेषण योग्य प्रोटीन -अणु ,जीवाणु-अणु एवं विषाणुओं के जैव- अणु भी ऐसी नियमित संरचनाएं लिए हों,यानी क्रिस्टलीय होवें ही , इसलिए एक्सरे -क्रिस्टलोग्रेफी की अपनी सीमाएं हैं, जिसमें प्राविधि में एक्स किरणें (एक्स -रे पुंज )अणुओं के रेगुलर पैटर्न से टकराकर विकीर्णित हो जाती हैं।
ट्रॅन्समिशन इलेक्ट्रॉन माइक्रोस्कोपी(TEM) का एक दोष और तब मुखरित होकर प्रकट होता है जब अन्वेषण के लिए लाये गए जैविक साम्पिल्स इलेक्ट्रॉन की उड़ान के लिए ज़रूरी वेक्यूम (निर्वात)में सूख कर बिखरने टूटने विखंडित होने लगते हैं।
क्रायो -ट्रॅन्समिशन इलेक्ट्रॉन माइक्रस्कोपी(Cryo-TEM) ने इन समस्याओं से निजात दिलवायी है और इसी काम के लिए इस बरस (२०१७ के लिए )रसायन विज्ञान का नोबेल पुरूस्कार इस पर काम करने वाले तीन विज्ञानियों में तकसीम किया गया है।
कौन से उपाय आज़माये गए ?
इन तीन विज्ञानियों में से एक हेंडरसन ने ग्लूकोज़ घोल का स्तेमाल किया ताकि साम्पिल्स सूखकर विखंडित न हो सकें।
डुबोशे ने साम्पिल्स को सूखने से बचाने के लिए हेंडरसन द्वारा अपनाई गई विधि का और परिष्कार किया। देखा गया कि हेंडरसन तकनीक उन जैविक साम्पिल्स के लिए काम नहीं करती है जो जल में घुलनशील रहतें हैं ,ऐसे में ये फ्रीज़ होने पर (प्रशीतित )होने पर आइस क्रिस्टल ही बना डालते हैं जो सोलुशन में ली गई छवियों के नष्ट होने से व्याख्यायित होने से रह जातीं हैं। जब छवियाँ ही विनष्ट हो जाएँ तो निष्कर्ष क्या निकाला जाए। वही ढाक के तीन पात।
डुबोशे ने क्या किया था ?
साम्पिल्स को इतनी द्रुतगति से प्रशीतित किया ,जल के अणु परम्परा गत नियमित संरचनाएं ही न बना सके।
और इसके साथ ही अब तक हमारी कोशिकाओं का अदृश्य बना रहा अगोचर संसार दृश्यमान हो उठा।
भविष्य अनेक संभावनाओं से सराबोर है
(१ )ड्रग -टारगेट्स का संरचनात्मक रेखांकन मुमकिन हो सकेगा।
(२ )हमारी कोशिकाओं के उन हिस्सों को भी खंगाला जा सकेगा जो हमें दर्द और गर्मी लगने का दवाब महसूस करने का एहसास करवाते हैं।
(३ )जैसे -जैसे Cryo-TEM की विभेदन क्षमता बढ़ती जायेगी ,बीमारियों को गहराई से बूझकर अभिनव दवाएं ईज़ाद की जा सकेंगी।
(४ )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.
(५ )जैव -रसायन एक नव -युग में प्रवेश कर सकता है निकट भविष्य में।
आँग्ल भाषा में सहज महसूस करने वाले उन जिज्ञासुओं के लिए जो विषय विस्तार में रूचि रखते हैं ,देखें उल्लेखित विशेष सामिग्री :
What is cryo-electron microscopy, the Nobel prize-winning technique?
The 2017 chemistry laureates were recognised for developing cryo-electron microscopy. But what is it, why is it exciting and where will it take us next?
A trio of scientists share this year’s Nobel prize for chemistry: Jacques Dubochet, Joachim Frank and Richard Henderson.
The technique has allowed scientists to study biological molecules such as the Zika virus in unprecedented details. Photograph: NobelPrize.org
Their win is for work on a technique known as cryo-electron microscopy that has allowed scientists to study biological molecules in unprecedented sharpness, not least the Zika virus and proteins thought to be involved in Alzheimer’s disease.
Being able to capture images of these biological molecules at atomic resolution not only helps scientists to understand their structures, but has opened up the possibility of exploring biological processes by stitching together images taken at different points in time.
Experts add that the information gleaned through cryo-electron microscopy has proved valuable in helping scientists to develop drugs. “It has been used in visualising the way in which antibodies can work to stop viruses being dangerous, leading to new ideas for medicines as just one example,” said Daniel Davis, professor of immunology at the University of Manchester.
Why do we need cryo-electron microscopy?
Microscopes allow scientists to look at structures that cannot be seen with the naked eye – but when these structures are very tiny, it is no longer possible to use rays of light to do the job because their wavelengths are not short enough. Instead, beams of electrons can be used – with a technique known as transmission electron microscopy (TEM) – or scientists can employ a method known as x-ray crystallography in which x-rays are scattered as they pass through samples, creating patterns that can be analysed to reveal the structure of molecules.
The trouble is, x-ray crystallography relies on biological molecules forming ordered structures, which many fail to do, and the technique does not allow researchers to probe how molecules move.
Historically, TEM also presented difficulties. The beam itself fried the biological molecules being studied, while the technique involved the use of a vacuum which resulted in biological molecules drying out and collapsing, throwing a spanner in the works when it came to probing their structure.
This year’s chemistry laureates tackled these conundrums, enabling scientists to use TEM to image biological molecules in incredible resolution.
What did they do?
Henderson and his team, using a glucose solution to prevent molecules drying out, combined a weaker beam of electrons with images taken from many angles and mathematical approaches to build up a 3D image of a protein neatly organised within a biological membrane. It was a breakthrough moment. Henderson later succeeded in unveiling its 3D structure at atomic resolution – a first for a protein.
Meanwhile Frank developed ingenious image processing techniques to unpick TEM data and build up images of biological molecules as they are in solution, where they point in many different directions.
Dubochet came up with a sophisticated approach to prevent molecules from drying out. Henderson’s technique did not work for water-soluble biological molecules, while freezing samples resulted in the formation of ice crystals which caused damage and made the resulting images challenging to interpret.
Dubochet’s solution was to rapidly cool samples at such speed that the water molecules did not have time to adopt a regular structure. Rather, they were left pointing every which way, resulting in a glass within which biological molecules were frozen in time – in their natural shape.
What’s next?
The trio’s work, and subsequent efforts to perfect these approaches, has already led to astonishing developments. “The technique of cryo-TEM has really opened up the molecular world of the cell to direct observation,” said Andrea Sella, professor of inorganic chemistry at University College London.
Among the processes it has made clearer is the mechanism by which DNA is copied into the single-stranded molecule RNA.
But the future is also exciting, with scientists using the technique to probe the structure of drug targets, as well as components within cells involved in sensing pain, temperature and pressure. Further improvements in resolution are also afoot.
“Cryo-electron microscopy is one of those techniques so basic and important that its use spans all of biology – including understanding the human body and human disease and in designing new medicines,” said Davis.
Nobel Prize in Chemistry 2017: Cryo-electron microscopy
The Nobel Prize in Chemistry 2017 goes to Jacques Dubochet, Joachim Frank, and Richard Henderson "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution."
Over the last few years, researchers have published atomic structures of numerous complicated protein complexes. (a) A protein complex that governs the circadian rhythm. (b) A sensor of the type that reads pressure changes in the ear and allows us to hear. (c) The Zika virus.
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.
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Materials provided by Nobel Foundation. Note: Content may be edited for style and length.
विशेष :
The visualization of chemistry and of life’s molecules—the shape of the needle that the Salmonella bacterium uses to attack cells, the surface of the Zika virus—has achieved a degree of splendor.
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