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Science Day 2013

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Govinda Bhisetti

Presentation prepared on 2013 Nobel Prizes and Science Breakthroughs for middle and high school students.

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Science Day 2013 for middle and high school children held on Friday, December 27, 2013 Govinda Bhisetti, Ph. D. govindab@gmail.com 9:30 ¨C 10:00 AM 10:00 ¨C 10:15 AM 10:15 ¨C 11:45 AM 12:00 ¨C 12:30 PM 12:30 ¨C 1:30 PM 1:30 ¨C 2:00 PM 2:00 ¨C 3:30 PM 3:30 ¨C 4:30 PM 12/27/2013 Arrival Introductions 2013 Nobel Prizes Breakthroughs in Science 2013 Lunch Year of Statistics 2013 Tribute to Thomas Bayes and C. R. Rao Group Discussion on Big Data Science Day Govinda Bhisetti 1
Nobel Prize "¡­The whole of my remaining realizable estate shall be dealt with in the following way: The capital (more than SEK 31 million, worth approximately SEK 1,702 million today ) shall be invested by my executors in safe securities and shall constitute a fund, the interest on which shall be annually distributed in the form of prizes to those who, during the preceding year, shall have conferred the greatest benefit on mankind ... ; one part to the person who shall have made the most important discovery within the domain of physiology or medicine; ... The prizes for ... shall be awarded by ... that for physiology or medicine by the Carolinska Institute in Stockholm; ... " Alfred Nobel's will, signed in Paris on 27 November 1895. The statutes of the Nobel Foundation, which were officially approved by the Swedish Government on 29 June 1900. This year's monetary award will be 8 million Swedish kronor (SEK) - about $1.2 million (same as in 2012). This represents a drop of 20%, compared with 2011 prize of 10 million SEK. 12/27/2013 Science Day Govinda Bhisetti 2
561 Nobel Prizes! From 1901 - 2013 Subject Prizes Laureates One Two Three Physics Chemistry Medicine Literature Peace Economics Total: 107 105 104 106 94 45 561 196 166 204 110 30 22 31 4 28 16 131 29 19 34 2 6 90 47 63 38 101 101+25 63 74 22 876 334 The average age of all Nobel Laureates in all prize categories between 1901 and 2013 is 59 years http://www.nobelprize.org/ 12/27/2013 Science Day Govinda Bhisetti 3
Prize Announcement Schedule ?? Monday, October 7, 2013 PHYSIOLOGY or MEDICINE ?? Tuesday, October 8, 2013 PHYSICS ?? Wednesday, October 9, 2013 ?? Thursday, October 10, 2013 ?? Friday, October 11, 2013 CHEMISTRY ?? Monday, October 14, 2013 ECONOMICS LITERATURE PEACE December 10, 2013: Nobel Prize Award Ceremony and the Nobel Banquet 12/27/2013 Science Day Govinda Bhisetti 4
2013 Nobel Prize winners 12/27/2013 Science Day Govinda Bhisetti 5
Literature Alice Munro ¡°master of the contemporary short story¡± Munro is acclaimed for her finely tuned storytelling. Her stories are often set in small town environments, where the struggle for a socially acceptable existence often results in strained relationships and moral conflicts ¨C problems that stem from generational differences and colliding life ambitions. Her texts often feature depictions of everyday but decisive events, epiphanies of a kind, that illuminate the surrounding story and let existential questions appear in a flash of lightning. 12/27/2013 Science Day Govinda Bhisetti 6
Peace Organization for the Prohibition of Chemical Weapons (OPCW) "for its extensive efforts to eliminate chemical weapons¡± 12/27/2013 Science Day Govinda Bhisetti 7
The Sveriges Riksbank Prize in Economic Sciences Eugene F. Fama, Lars Peter Hansen and Robert J. Shiller ¡±for their empirical analysis of asset prices¡± Fama and Shiller, leading proponents of opposing views about the rationality of financial markets ¡ª a dispute with important implications for investment strategy, financial regulation and economic policy ¡ª were joined in unlikely union as winners of the Nobel Memorial Prize in Economic Science. http://www.pbs.org/newshour/bb/business/july-dec13/economist_12-11.html 12/27/2013 Science Day Govinda Bhisetti 8
PHYSIOLOGY or MEDICINE James E. Rothman, Randy W.Schekman and Thomas C. Sudhof ¡°for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells¡± http://www.youtube.com/watch?v=PORJ086kT4s 12/27/2013 Science Day Govinda Bhisetti 9
Vesicle Transport ER: http://www.youtube.com/watch?v=faE3STnfIGs Golgi: http://www.youtube.com/watch?v=OOSDP6DWwL4 Receptor mediated endocytosis: http://www.youtube.com/watch?v=PifagmJRLZ0 12/27/2013 Science Day Govinda Bhisetti 10
Vesicle formation Nobel Physics interview:Vesicle Dance: Vesic V Vesicular Dance: http://www.youtube.com/watch?v=BdKbRgT4hn8 Clathrin¡¯s role: http://www.youtube.com/watch?v=-ZFnO5RY1cU 12/27/2013 Science Day Govinda Bhisetti 11
Ivacaftor: a recent drug targeting defective CFTR ¨C a Cl ion transporter Golgi ER CFTR animation: http://www.youtube.com/watch?v=_j99-xgOIaw Kalydeco: http://www.youtube.com/watch?v=AHJ5ZroGhKk 12/27/2013 Science Day Govinda Bhisetti 12
CHEMISTRY Martin Karplus, Michael Levitt and Ariel Warshel "for the development of multiscale models for complex chemical systems" Nobelprizes: http://www.nobelprize.org/mediaplayer/index.php?id=1957 12/27/2013 Science Day Govinda Bhisetti 13
Multi Scale Simulations: MM + QM ¡°¡­everything that living things do can be understood in terms of the jigglings and wigglings of atoms.¡± -?The Feynmann Lectures (1963) Molecular Dynamics: http://www.youtube.com/watch?v=lLFEqKl3sm4 Simulation of chemical Reactions : http://www.youtube.com/watch?v=CqQfmmz8vjM 12/27/2013 Science Day Govinda Bhisetti 14
Application of Computer Simulations in Drug Discovery HIV Protease ¨C amprenavir 12/27/2013 HCV Protease - telaprevir Science Day Govinda Bhisetti 15
PHYSICS? ? Francois Englert and Peter Higgs? "for the theoretical discovery of a mechanism that contributes to our understanding of the origin of mass of subatomic particles¡± http://www.youtube.com/watch?v=RIg1Vh7uPyw (July 7, 2011) http://www.nytimes.com/video/science/100000002094542/higgs-boson-a-cern-collision-course.html (July 4, 2012) 12/27/2013 Science Day Govinda Bhisetti 16
Particle Physics - Key Discoveries 1802: John Dalton lays the groundwork for modern atomic theory. 1897: The electron is discovered by Joseph Thomson. 1899-1919: Ernest Rutherford identifies the atomic nucleus, the proton, and alpha and beta particles. 1932: The neutron is discovered by James Chadwick of Britain. The first antiparticle, the positron (the mirror particle to the electron), is discovered by Carl Anderson. 1934: Enrico Fermi postulates the existence of the neutrino, a neutral-charge partner to the electron. The theory is confirmed in 1959. 1964: Within months of each other, six physicists publish the theory of a subatomic particle providing mass to matter: First to publish were Francois Englert and Robert Brout, followed by Peter Higgs, and then the team of Dick Hagen, Gerald Guralnik and Tom Kibble. Murray Gell-Mann and George Zweig proposed that protons and neutrons are comprised of quarks. 1974: The Standard Model of physics is devised: a theory that everything in the Universe is made up of 12 building-block particles governed by four fundamental forces. The theory cannot work without the Higgs boson conferring mass on matter, as the fundamental particles by their very nature do not have mass of their own. Standard Model of Particle Physics: http://www.youtube.com/watch?v=V0KjXsGRvoA 1977-2000: A flurry of discoveries strengthens the Standard Model hypothesis, including the existence of several quarks and leptons (the two types of fundamental particles), the tau neutrino and W and Z bosons that help carry the "weak" force. 2008: The European Organization for Nuclear Research (CERN) starts up the Large Hadron Collider (LHC), the world's biggest particle smasher. 2012 (July 4): CERN announces it has discovered a particle that resembles the Higgs. New data analysed since then has given rise to increasing scientific certainty that the discovery is indeed the elusive "God particle", as the boson is also known. 2012 Breakthrough: http://video.sciencemag.org/SciOriginals/2047901580001/1/@btoy2012 2013: Higgs and Englert are awarded the Nobel Prize in Physics for their conception of the particle. 12/27/2013 Science Day Govinda Bhisetti 17
Higgs Boson Detected Announced on July 4, 2012 12/27/2013 Science Day Govinda Bhisetti 18
TED talk before the next section http://www.ted.com/talks/peter_doolittle_how_your_working_memory_makes_sense_of_the_world.html Students to remember 3 or 4 of the 10 Science Breakthroughs after the next section 12/27/2013 Science Day Govinda Bhisetti 19
Breakthrough of the Year 2013 1. Cancer Immunotherapy 2. CRISPR 3. CLARITY 4. Human Stem Cells from Cloning 5. Mini-Organs 6. Cosmic Particle Accelerators 7. Perovskites Solar Cells 8. Why We Sleep 9. Our Microbes, Our Health 10. In Vaccine Design, Looks Do Matter 23 December 2011 12/27/2013 Science Day Govinda Bhisetti 20
10. In Vaccine Design, Looks Do Matter Structure Biology to design a ¡°better¡± vaccine against RSV Respiratory syncytial virus (RSV) hospitalizes millions of infants each year with pneumonia and other lung diseases, and it has defied many a vaccine developer. RSV kills 160,000 kids each year. RSV has a protein on its surface, known as F, that orchestrates its fusion with cells during the infection process. The flexible F protein has two distinct shapes, coiled up before it fuses and ¡°sprung¡± afterwards. This spring, it is reported in Science (31 May, p. 1113) the crystal structure of a potent antibody bound to the prefusion F structure, spotlighting a site on the virus that was especially vulnerable to neutralization. The RSV F protein displays the red area needed to trigger potent antibodies in its coiled state (left). In November, the same group described the next step: used their structure to design an RSV F protein that could serve as an immunogen (the main ingredient of a vaccine). 12/27/2013 Science Day Govinda Bhisetti Hot spot. An antibody (black) can cripple RSV by binding to a vulnerable site (white) on its F protein in its coiled state. 21
9. Our microbes, Our Health Role of Bacteria living inside human body In 2008, nearly 300,000 infants in China got kidney stones from milk formula tainted with melamine, a plastics additive that was used illegally to bulk up the formula's apparent protein content. This year, scientists found that a bacterium (Klebsiella) may be to blame. In Malawi, researchers studied unusual cases in which one twin developed a malnutrition syndrome called Kwashiorkor but the other did not. They discovered that the malnourished children's microbial portfolio had not matured properly. This year, researchers traced several links between gut microbes and cancer. Three anticancer therapies proved to need gut bacteria to be effective; the bacteria help prime the immune system to respond to drug treatment. A gut bacterium called Fusobacterium plays a role in stimulating colorectal tumors. 12/27/2013 Science Day Govinda Bhisetti 22
8. Why We Sleep ¡­Sleep helps to restore and repair the brain Most researchers agree that sleep serves many purposes, such as bolstering the immune system and consolidating memories, but they have long sought a "core" function common to species that sleep. By tracking colored dye through the brains of sleeping mice, scientists got what they think is a direct view of sleep's basic purpose: cleaning the brain. When mice slumber, they found, a network of transport channels through the brain expands by 60%, increasing the flow of cerebral spinal fluid. The surge of fluid clears away metabolic waste products such as ¦Â amyloid proteins. Brainwashing. Fluid-filled channels (pale blue) between neurons expand and flush out waste while mice sleep. 12/27/2013 Science Day Govinda Bhisetti 23
7. Perovskite Solar Cells ¡­New solar cell materials made rapid progress Cheap, easy-to-make crystals called perovskites proved capable of converting more than 15% of the energy in sunlight to electricity. That's up from 3.8% just 4 years ago. Silicon solar cells (20% efficiency) rely on semiconductors that must be grown at high temperatures in expensive fabrication facilities. Perovskites are made simply by mixing inexpensive precursor compounds in solution and then drying them on a surface. Perovskites excel at snagging the higher energy photons in sunlight¡ªthe blues and greens¡ªwhile silicon does better at grabbing the lower energy red and infrared photons. http://www.sciencemag.org/content/342/6160/794/suppl/DC1 http://www.youtube.com/watch?v=qmH79bB1V7E 12/27/2013 Challenges: Solar cell perovskites are fragile and readily break down when exposed to water or air. Also, the current varieties contain lead. Science Day Govinda Bhisetti 24
6. Cosmic Particle Accelerators Birthplaces of cosmic rays traced to remnants of supernovae Boom! Supernova remnants such as the Jellyfish Nebula can boost particles to enormous energies 12/27/2013 NASA's orbiting Fermi Gamma-ray Space Telescope produced the first direct evidence of high energy particles revving up in cloudlike supernova remnants within our galaxy. When a star explodes, material ejected from it crashes into a tenuous sea of gas between the stars. That interstellar medium is so thin that few particles collide directly. However, particles from the supernova can rebound off magnetic fields in space, and slingshot other particles to higher energies. As particles circulate repeatedly through such a shock, they may accelerate to colossal energies¡ªhundreds of times higher than particle accelerators have reached. However, the highest energy cosmic rays originate from other sources outside our galaxy. Science Day Govinda Bhisetti 25
5. Dishing Up Mini-Organs Pluripotent stem cells are coaxed to grow into tiny ¡°organoids¡± Self-organized. A cross section of a lab-grown mini-brain shows neural stem cells (red) and neurons (green) 12/27/2013 Left alone in a lab dish, pluripotent stem cells run riot. They differentiate into a disorganized mass of tissues: beating heart cells, neurons, even hair and teeth. This year, researchers succeeded in coaxing stems cells to grow into a variety of specific "organoids" in the lab: liver buds, mini-kidneys, and, most remarkably, rudimentary human brains. The brains, grown by Austrian researchers, differ in important ways from the real thing. Because they have no blood supply, they stop growing once they reach the size of an apple seed. Cells at the core, starved of oxygen and other nutrients, die off. But the organoids mimic developing human brains to a surprising degree, under the microscope, resemble those in the brain of an early human fetus. The mini-brains have already yielded insights into microcephaly, a condition in which the brain doesn't grow to its full size. Science Day Govinda Bhisetti 26
4. Human Stem Cells from Cloning Stem cells are derived from closed human embryos This year, researchers cloned human embryos and used them as a source of embryonic stem (ES) cells. The cloning technique, called somatic cell nuclear transfer (SCNT), is the same one used to clone Dolly the sheep 17 years ago. Scientists remove the nucleus from an egg cell and then fuse the remaining cell material with a cell from the individual to be cloned. Patient-specific stem cells can be made by "reprogramming" adult cells into induced pluripotent stem (iPS) cells¡­ a less controversial and less expensive approach. Long-sought. Cloned human embryos, which can be used to make patient-specific stem cell lines 12/27/2013 Now, investigators will be able to compare the two types of human stem cells side by side. Science Day Govinda Bhisetti 27
3. CLARITY Makes It Perfectly Clear An imaging technique turns brain tissue transparent CLARITY turns brain tissue as transparent as glass by removing the fatty, light-scattering lipid molecules that form cellular membranes. It replaces the lipids with molecules of a clear gel but leaves all neurons, other brain cells, and their organelles intact, putting the intricacies of the brain on display. The advance could speed up by 100fold tasks such as counting all the neurons in a given brain region. Crystal clear. A new method of making tissue transparent will help neuroscientists explore the postmortem brain in 3D. 12/27/2013 At present, however, the technique is limited to small amounts of tissue: Just clarifying a 4-mm-diameter mouse brain takes about 9 days. Science Day Govinda Bhisetti 28
2. CRISPR Genetic microsurgery for masses CRISPR - Clustered Regularly Interspaced Short Palindromic Repeats A bacterial protein called Cas9, coupled with RNA designed to home in on specific DNA sequences, gives researchers the equivalent of a molecular surgery kit for routinely disabling, activating, or changing genes. Molecular scalpel. To home in on the right DNA, the Cas9 protein links up with guide RNA that has a target-specific sequence. Once attached, Cas9 has two active sites that cut the DNA in the right place. 12/27/2013 This technology has become red hot in the past year, with more than 50 publications in 10 months. Since January, more than a dozen teams have manipulated specific genes in mice, rats, bacteria, yeast, zebrafish, nematodes, fruit flies, plants, and human cells, paving the way for understanding how these genes function and possibly harnessing them to improve health. One team even reported using the approach to disable HIV hiding in T cells. Science Day Govinda Bhisetti 29
1. Cancer Immunotherapy Harnessing the immune system to battle tumors. Immunotherapy marks an entirely different way of treating cancer¡ªby targeting the immune system, not the tumor itself. A new protein receptor on the surface of T cells, called cytotoxic T-lymphocyte antigen 4, or CTLA-4 (discovered in 1987) puts the brakes on T cells, preventing them from launching full-out immune attacks. Blocking the blocker¡ª the CTLA-4 molecule¡ªwould set the immune system free to destroy cancer. An antibody against CTLA-4 erased tumors in mice(1996). In 2011, BMS reported that patients with metastatic melanoma lived an average of 10 months on the antibody, compared with 6 months without it. Nearly a quarter of participants survived at least 2 years. Better results were obtained with anti-PD1 (another T cell brake) antibody. CAR (Chimeric Antigen Receptor) therapy¡ªa personalized treatment that involves genetically modifying a patient's T cells to make them target tumor cells was introduced in 2010 and is showing encouraging results. Domino effect. One such treatment, with the antibody in pink at the top, works by blocking a protein receptor, in purple, on a T cell. That sets off a chain reaction that allows Video: T cells to target a tumor cell (bottom left). http://www.sciencemag.org/content/342/6165/1432.full 12/27/2013 Science Day Govinda Bhisetti 30
Lunch Break 12/27/2013 Science Day Govinda Bhisetti 31
Year of Statistics 2013 http://www.statistics2013.org/ Tribute to Thomas Bayes and C. R. Rao Statistical thinking will one day be as necessary for efficient citizenship as the ability to read and write. - H. G. Wells C. R. Rao going strong at 93! - A giant among Indian Statisticans Thomas Bayes 1701-1761 250 Years of Bayes Theorem What is Statistics? The science of learning from (or making sense out of) data The theory and methods of extracting information from observational data The science of uncertainty The quintessential interdisciplinary science The art of telling a story with [numerical] data Applied to many areas that touch your life: -? Medicine, Science, Agriculture, Economics, Business, Law, Weather http://www.math.harvard.edu/~knill/mathmovies/m4v/numb3rs_pilot.webm 12/27/2013 Science Day Govinda Bhisetti 32
Tribute to Dr. C. R. Rao 2011 Royal Statistical Soceity Guy Medal in Gold ¨¨? http://www.youtube.com/watch?v=f6b8GxjBRG4 12/27/2013 Science Day Govinda Bhisetti 33
12/27/2013 Science Day Govinda Bhisetti 34
Bayes¡¯ Theorem A theorem of probability theory by Thomas Bayes Bayes: How one equation changed the the way I think: http://www.youtube.com/watch?v=za7RqnT7CM0 http://www.youtube.com/watch?v=U9-G-noZrwc https://www.khanacademy.org/math/applied-math/cryptography/random-algorithms-probability/v/bayes-theorem-visualized 12/27/2013 Science Day Govinda Bhisetti 35
Naked Statistics by Charles Wheelan http://www.youtube.com/watch?v=cIbr_AksnAc 12/27/2013 Science Day Govinda Bhisetti 36
Stats that reshape your world view: Rosling http://www.youtube.com/watch?v=hVimVzgtD6w 12/27/2013 Science Day Govinda Bhisetti 37
Group Discussion: Big Data and Data Scientists ¨C growth area for STEM careers http://drewconway.com/zia/2013/3/26/the-data-science-venn-diagram 12/27/2013 Science Day Govinda Bhisetti 38

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Science Day 2013

  • 1. Science Day 2013 for middle and high school children held on Friday, December 27, 2013 Govinda Bhisetti, Ph. D. govindab@gmail.com 9:30 ¨C 10:00 AM 10:00 ¨C 10:15 AM 10:15 ¨C 11:45 AM 12:00 ¨C 12:30 PM 12:30 ¨C 1:30 PM 1:30 ¨C 2:00 PM 2:00 ¨C 3:30 PM 3:30 ¨C 4:30 PM 12/27/2013 Arrival Introductions 2013 Nobel Prizes Breakthroughs in Science 2013 Lunch Year of Statistics 2013 Tribute to Thomas Bayes and C. R. Rao Group Discussion on Big Data Science Day Govinda Bhisetti 1
  • 2. Nobel Prize "¡­The whole of my remaining realizable estate shall be dealt with in the following way: The capital (more than SEK 31 million, worth approximately SEK 1,702 million today ) shall be invested by my executors in safe securities and shall constitute a fund, the interest on which shall be annually distributed in the form of prizes to those who, during the preceding year, shall have conferred the greatest benefit on mankind ... ; one part to the person who shall have made the most important discovery within the domain of physiology or medicine; ... The prizes for ... shall be awarded by ... that for physiology or medicine by the Carolinska Institute in Stockholm; ... " Alfred Nobel's will, signed in Paris on 27 November 1895. The statutes of the Nobel Foundation, which were officially approved by the Swedish Government on 29 June 1900. This year's monetary award will be 8 million Swedish kronor (SEK) - about $1.2 million (same as in 2012). This represents a drop of 20%, compared with 2011 prize of 10 million SEK. 12/27/2013 Science Day Govinda Bhisetti 2
  • 3. 561 Nobel Prizes! From 1901 - 2013 Subject Prizes Laureates One Two Three Physics Chemistry Medicine Literature Peace Economics Total: 107 105 104 106 94 45 561 196 166 204 110 30 22 31 4 28 16 131 29 19 34 2 6 90 47 63 38 101 101+25 63 74 22 876 334 The average age of all Nobel Laureates in all prize categories between 1901 and 2013 is 59 years http://www.nobelprize.org/ 12/27/2013 Science Day Govinda Bhisetti 3
  • 4. Prize Announcement Schedule ?? Monday, October 7, 2013 PHYSIOLOGY or MEDICINE ?? Tuesday, October 8, 2013 PHYSICS ?? Wednesday, October 9, 2013 ?? Thursday, October 10, 2013 ?? Friday, October 11, 2013 CHEMISTRY ?? Monday, October 14, 2013 ECONOMICS LITERATURE PEACE December 10, 2013: Nobel Prize Award Ceremony and the Nobel Banquet 12/27/2013 Science Day Govinda Bhisetti 4
  • 5. 2013 Nobel Prize winners 12/27/2013 Science Day Govinda Bhisetti 5
  • 6. Literature Alice Munro ¡°master of the contemporary short story¡± Munro is acclaimed for her finely tuned storytelling. Her stories are often set in small town environments, where the struggle for a socially acceptable existence often results in strained relationships and moral conflicts ¨C problems that stem from generational differences and colliding life ambitions. Her texts often feature depictions of everyday but decisive events, epiphanies of a kind, that illuminate the surrounding story and let existential questions appear in a flash of lightning. 12/27/2013 Science Day Govinda Bhisetti 6
  • 7. Peace Organization for the Prohibition of Chemical Weapons (OPCW) "for its extensive efforts to eliminate chemical weapons¡± 12/27/2013 Science Day Govinda Bhisetti 7
  • 8. The Sveriges Riksbank Prize in Economic Sciences Eugene F. Fama, Lars Peter Hansen and Robert J. Shiller ¡±for their empirical analysis of asset prices¡± Fama and Shiller, leading proponents of opposing views about the rationality of financial markets ¡ª a dispute with important implications for investment strategy, financial regulation and economic policy ¡ª were joined in unlikely union as winners of the Nobel Memorial Prize in Economic Science. http://www.pbs.org/newshour/bb/business/july-dec13/economist_12-11.html 12/27/2013 Science Day Govinda Bhisetti 8
  • 9. PHYSIOLOGY or MEDICINE James E. Rothman, Randy W.Schekman and Thomas C. Sudhof ¡°for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells¡± http://www.youtube.com/watch?v=PORJ086kT4s 12/27/2013 Science Day Govinda Bhisetti 9
  • 10. Vesicle Transport ER: http://www.youtube.com/watch?v=faE3STnfIGs Golgi: http://www.youtube.com/watch?v=OOSDP6DWwL4 Receptor mediated endocytosis: http://www.youtube.com/watch?v=PifagmJRLZ0 12/27/2013 Science Day Govinda Bhisetti 10
  • 11. Vesicle formation Nobel Physics interview:Vesicle Dance: Vesic V Vesicular Dance: http://www.youtube.com/watch?v=BdKbRgT4hn8 Clathrin¡¯s role: http://www.youtube.com/watch?v=-ZFnO5RY1cU 12/27/2013 Science Day Govinda Bhisetti 11
  • 12. Ivacaftor: a recent drug targeting defective CFTR ¨C a Cl ion transporter Golgi ER CFTR animation: http://www.youtube.com/watch?v=_j99-xgOIaw Kalydeco: http://www.youtube.com/watch?v=AHJ5ZroGhKk 12/27/2013 Science Day Govinda Bhisetti 12
  • 13. CHEMISTRY Martin Karplus, Michael Levitt and Ariel Warshel "for the development of multiscale models for complex chemical systems" Nobelprizes: http://www.nobelprize.org/mediaplayer/index.php?id=1957 12/27/2013 Science Day Govinda Bhisetti 13
  • 14. Multi Scale Simulations: MM + QM ¡°¡­everything that living things do can be understood in terms of the jigglings and wigglings of atoms.¡± -?The Feynmann Lectures (1963) Molecular Dynamics: http://www.youtube.com/watch?v=lLFEqKl3sm4 Simulation of chemical Reactions : http://www.youtube.com/watch?v=CqQfmmz8vjM 12/27/2013 Science Day Govinda Bhisetti 14
  • 15. Application of Computer Simulations in Drug Discovery HIV Protease ¨C amprenavir 12/27/2013 HCV Protease - telaprevir Science Day Govinda Bhisetti 15
  • 16. PHYSICS? ? Francois Englert and Peter Higgs? "for the theoretical discovery of a mechanism that contributes to our understanding of the origin of mass of subatomic particles¡± http://www.youtube.com/watch?v=RIg1Vh7uPyw (July 7, 2011) http://www.nytimes.com/video/science/100000002094542/higgs-boson-a-cern-collision-course.html (July 4, 2012) 12/27/2013 Science Day Govinda Bhisetti 16
  • 17. Particle Physics - Key Discoveries 1802: John Dalton lays the groundwork for modern atomic theory. 1897: The electron is discovered by Joseph Thomson. 1899-1919: Ernest Rutherford identifies the atomic nucleus, the proton, and alpha and beta particles. 1932: The neutron is discovered by James Chadwick of Britain. The first antiparticle, the positron (the mirror particle to the electron), is discovered by Carl Anderson. 1934: Enrico Fermi postulates the existence of the neutrino, a neutral-charge partner to the electron. The theory is confirmed in 1959. 1964: Within months of each other, six physicists publish the theory of a subatomic particle providing mass to matter: First to publish were Francois Englert and Robert Brout, followed by Peter Higgs, and then the team of Dick Hagen, Gerald Guralnik and Tom Kibble. Murray Gell-Mann and George Zweig proposed that protons and neutrons are comprised of quarks. 1974: The Standard Model of physics is devised: a theory that everything in the Universe is made up of 12 building-block particles governed by four fundamental forces. The theory cannot work without the Higgs boson conferring mass on matter, as the fundamental particles by their very nature do not have mass of their own. Standard Model of Particle Physics: http://www.youtube.com/watch?v=V0KjXsGRvoA 1977-2000: A flurry of discoveries strengthens the Standard Model hypothesis, including the existence of several quarks and leptons (the two types of fundamental particles), the tau neutrino and W and Z bosons that help carry the "weak" force. 2008: The European Organization for Nuclear Research (CERN) starts up the Large Hadron Collider (LHC), the world's biggest particle smasher. 2012 (July 4): CERN announces it has discovered a particle that resembles the Higgs. New data analysed since then has given rise to increasing scientific certainty that the discovery is indeed the elusive "God particle", as the boson is also known. 2012 Breakthrough: http://video.sciencemag.org/SciOriginals/2047901580001/1/@btoy2012 2013: Higgs and Englert are awarded the Nobel Prize in Physics for their conception of the particle. 12/27/2013 Science Day Govinda Bhisetti 17
  • 18. Higgs Boson Detected Announced on July 4, 2012 12/27/2013 Science Day Govinda Bhisetti 18
  • 19. TED talk before the next section http://www.ted.com/talks/peter_doolittle_how_your_working_memory_makes_sense_of_the_world.html Students to remember 3 or 4 of the 10 Science Breakthroughs after the next section 12/27/2013 Science Day Govinda Bhisetti 19
  • 20. Breakthrough of the Year 2013 1. Cancer Immunotherapy 2. CRISPR 3. CLARITY 4. Human Stem Cells from Cloning 5. Mini-Organs 6. Cosmic Particle Accelerators 7. Perovskites Solar Cells 8. Why We Sleep 9. Our Microbes, Our Health 10. In Vaccine Design, Looks Do Matter 23 December 2011 12/27/2013 Science Day Govinda Bhisetti 20
  • 21. 10. In Vaccine Design, Looks Do Matter Structure Biology to design a ¡°better¡± vaccine against RSV Respiratory syncytial virus (RSV) hospitalizes millions of infants each year with pneumonia and other lung diseases, and it has defied many a vaccine developer. RSV kills 160,000 kids each year. RSV has a protein on its surface, known as F, that orchestrates its fusion with cells during the infection process. The flexible F protein has two distinct shapes, coiled up before it fuses and ¡°sprung¡± afterwards. This spring, it is reported in Science (31 May, p. 1113) the crystal structure of a potent antibody bound to the prefusion F structure, spotlighting a site on the virus that was especially vulnerable to neutralization. The RSV F protein displays the red area needed to trigger potent antibodies in its coiled state (left). In November, the same group described the next step: used their structure to design an RSV F protein that could serve as an immunogen (the main ingredient of a vaccine). 12/27/2013 Science Day Govinda Bhisetti Hot spot. An antibody (black) can cripple RSV by binding to a vulnerable site (white) on its F protein in its coiled state. 21
  • 22. 9. Our microbes, Our Health Role of Bacteria living inside human body In 2008, nearly 300,000 infants in China got kidney stones from milk formula tainted with melamine, a plastics additive that was used illegally to bulk up the formula's apparent protein content. This year, scientists found that a bacterium (Klebsiella) may be to blame. In Malawi, researchers studied unusual cases in which one twin developed a malnutrition syndrome called Kwashiorkor but the other did not. They discovered that the malnourished children's microbial portfolio had not matured properly. This year, researchers traced several links between gut microbes and cancer. Three anticancer therapies proved to need gut bacteria to be effective; the bacteria help prime the immune system to respond to drug treatment. A gut bacterium called Fusobacterium plays a role in stimulating colorectal tumors. 12/27/2013 Science Day Govinda Bhisetti 22
  • 23. 8. Why We Sleep ¡­Sleep helps to restore and repair the brain Most researchers agree that sleep serves many purposes, such as bolstering the immune system and consolidating memories, but they have long sought a "core" function common to species that sleep. By tracking colored dye through the brains of sleeping mice, scientists got what they think is a direct view of sleep's basic purpose: cleaning the brain. When mice slumber, they found, a network of transport channels through the brain expands by 60%, increasing the flow of cerebral spinal fluid. The surge of fluid clears away metabolic waste products such as ¦Â amyloid proteins. Brainwashing. Fluid-filled channels (pale blue) between neurons expand and flush out waste while mice sleep. 12/27/2013 Science Day Govinda Bhisetti 23
  • 24. 7. Perovskite Solar Cells ¡­New solar cell materials made rapid progress Cheap, easy-to-make crystals called perovskites proved capable of converting more than 15% of the energy in sunlight to electricity. That's up from 3.8% just 4 years ago. Silicon solar cells (20% efficiency) rely on semiconductors that must be grown at high temperatures in expensive fabrication facilities. Perovskites are made simply by mixing inexpensive precursor compounds in solution and then drying them on a surface. Perovskites excel at snagging the higher energy photons in sunlight¡ªthe blues and greens¡ªwhile silicon does better at grabbing the lower energy red and infrared photons. http://www.sciencemag.org/content/342/6160/794/suppl/DC1 http://www.youtube.com/watch?v=qmH79bB1V7E 12/27/2013 Challenges: Solar cell perovskites are fragile and readily break down when exposed to water or air. Also, the current varieties contain lead. Science Day Govinda Bhisetti 24
  • 25. 6. Cosmic Particle Accelerators Birthplaces of cosmic rays traced to remnants of supernovae Boom! Supernova remnants such as the Jellyfish Nebula can boost particles to enormous energies 12/27/2013 NASA's orbiting Fermi Gamma-ray Space Telescope produced the first direct evidence of high energy particles revving up in cloudlike supernova remnants within our galaxy. When a star explodes, material ejected from it crashes into a tenuous sea of gas between the stars. That interstellar medium is so thin that few particles collide directly. However, particles from the supernova can rebound off magnetic fields in space, and slingshot other particles to higher energies. As particles circulate repeatedly through such a shock, they may accelerate to colossal energies¡ªhundreds of times higher than particle accelerators have reached. However, the highest energy cosmic rays originate from other sources outside our galaxy. Science Day Govinda Bhisetti 25
  • 26. 5. Dishing Up Mini-Organs Pluripotent stem cells are coaxed to grow into tiny ¡°organoids¡± Self-organized. A cross section of a lab-grown mini-brain shows neural stem cells (red) and neurons (green) 12/27/2013 Left alone in a lab dish, pluripotent stem cells run riot. They differentiate into a disorganized mass of tissues: beating heart cells, neurons, even hair and teeth. This year, researchers succeeded in coaxing stems cells to grow into a variety of specific "organoids" in the lab: liver buds, mini-kidneys, and, most remarkably, rudimentary human brains. The brains, grown by Austrian researchers, differ in important ways from the real thing. Because they have no blood supply, they stop growing once they reach the size of an apple seed. Cells at the core, starved of oxygen and other nutrients, die off. But the organoids mimic developing human brains to a surprising degree, under the microscope, resemble those in the brain of an early human fetus. The mini-brains have already yielded insights into microcephaly, a condition in which the brain doesn't grow to its full size. Science Day Govinda Bhisetti 26
  • 27. 4. Human Stem Cells from Cloning Stem cells are derived from closed human embryos This year, researchers cloned human embryos and used them as a source of embryonic stem (ES) cells. The cloning technique, called somatic cell nuclear transfer (SCNT), is the same one used to clone Dolly the sheep 17 years ago. Scientists remove the nucleus from an egg cell and then fuse the remaining cell material with a cell from the individual to be cloned. Patient-specific stem cells can be made by "reprogramming" adult cells into induced pluripotent stem (iPS) cells¡­ a less controversial and less expensive approach. Long-sought. Cloned human embryos, which can be used to make patient-specific stem cell lines 12/27/2013 Now, investigators will be able to compare the two types of human stem cells side by side. Science Day Govinda Bhisetti 27
  • 28. 3. CLARITY Makes It Perfectly Clear An imaging technique turns brain tissue transparent CLARITY turns brain tissue as transparent as glass by removing the fatty, light-scattering lipid molecules that form cellular membranes. It replaces the lipids with molecules of a clear gel but leaves all neurons, other brain cells, and their organelles intact, putting the intricacies of the brain on display. The advance could speed up by 100fold tasks such as counting all the neurons in a given brain region. Crystal clear. A new method of making tissue transparent will help neuroscientists explore the postmortem brain in 3D. 12/27/2013 At present, however, the technique is limited to small amounts of tissue: Just clarifying a 4-mm-diameter mouse brain takes about 9 days. Science Day Govinda Bhisetti 28
  • 29. 2. CRISPR Genetic microsurgery for masses CRISPR - Clustered Regularly Interspaced Short Palindromic Repeats A bacterial protein called Cas9, coupled with RNA designed to home in on specific DNA sequences, gives researchers the equivalent of a molecular surgery kit for routinely disabling, activating, or changing genes. Molecular scalpel. To home in on the right DNA, the Cas9 protein links up with guide RNA that has a target-specific sequence. Once attached, Cas9 has two active sites that cut the DNA in the right place. 12/27/2013 This technology has become red hot in the past year, with more than 50 publications in 10 months. Since January, more than a dozen teams have manipulated specific genes in mice, rats, bacteria, yeast, zebrafish, nematodes, fruit flies, plants, and human cells, paving the way for understanding how these genes function and possibly harnessing them to improve health. One team even reported using the approach to disable HIV hiding in T cells. Science Day Govinda Bhisetti 29
  • 30. 1. Cancer Immunotherapy Harnessing the immune system to battle tumors. Immunotherapy marks an entirely different way of treating cancer¡ªby targeting the immune system, not the tumor itself. A new protein receptor on the surface of T cells, called cytotoxic T-lymphocyte antigen 4, or CTLA-4 (discovered in 1987) puts the brakes on T cells, preventing them from launching full-out immune attacks. Blocking the blocker¡ª the CTLA-4 molecule¡ªwould set the immune system free to destroy cancer. An antibody against CTLA-4 erased tumors in mice(1996). In 2011, BMS reported that patients with metastatic melanoma lived an average of 10 months on the antibody, compared with 6 months without it. Nearly a quarter of participants survived at least 2 years. Better results were obtained with anti-PD1 (another T cell brake) antibody. CAR (Chimeric Antigen Receptor) therapy¡ªa personalized treatment that involves genetically modifying a patient's T cells to make them target tumor cells was introduced in 2010 and is showing encouraging results. Domino effect. One such treatment, with the antibody in pink at the top, works by blocking a protein receptor, in purple, on a T cell. That sets off a chain reaction that allows Video: T cells to target a tumor cell (bottom left). http://www.sciencemag.org/content/342/6165/1432.full 12/27/2013 Science Day Govinda Bhisetti 30
  • 31. Lunch Break 12/27/2013 Science Day Govinda Bhisetti 31
  • 32. Year of Statistics 2013 http://www.statistics2013.org/ Tribute to Thomas Bayes and C. R. Rao Statistical thinking will one day be as necessary for efficient citizenship as the ability to read and write. - H. G. Wells C. R. Rao going strong at 93! - A giant among Indian Statisticans Thomas Bayes 1701-1761 250 Years of Bayes Theorem What is Statistics? The science of learning from (or making sense out of) data The theory and methods of extracting information from observational data The science of uncertainty The quintessential interdisciplinary science The art of telling a story with [numerical] data Applied to many areas that touch your life: -? Medicine, Science, Agriculture, Economics, Business, Law, Weather http://www.math.harvard.edu/~knill/mathmovies/m4v/numb3rs_pilot.webm 12/27/2013 Science Day Govinda Bhisetti 32
  • 33. Tribute to Dr. C. R. Rao 2011 Royal Statistical Soceity Guy Medal in Gold ¨¨? http://www.youtube.com/watch?v=f6b8GxjBRG4 12/27/2013 Science Day Govinda Bhisetti 33
  • 35. Bayes¡¯ Theorem A theorem of probability theory by Thomas Bayes Bayes: How one equation changed the the way I think: http://www.youtube.com/watch?v=za7RqnT7CM0 http://www.youtube.com/watch?v=U9-G-noZrwc https://www.khanacademy.org/math/applied-math/cryptography/random-algorithms-probability/v/bayes-theorem-visualized 12/27/2013 Science Day Govinda Bhisetti 35
  • 36. Naked Statistics by Charles Wheelan http://www.youtube.com/watch?v=cIbr_AksnAc 12/27/2013 Science Day Govinda Bhisetti 36
  • 37. Stats that reshape your world view: Rosling http://www.youtube.com/watch?v=hVimVzgtD6w 12/27/2013 Science Day Govinda Bhisetti 37
  • 38. Group Discussion: Big Data and Data Scientists ¨C growth area for STEM careers http://drewconway.com/zia/2013/3/26/the-data-science-venn-diagram 12/27/2013 Science Day Govinda Bhisetti 38