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Statewide website to help match veterans with careers in Indiana

first_imgStatewide—Indiana Lt. Governor Suzanne Crouch and INvets announced today the next-generation website, INvets.org – to connect veterans directly with Hoosier companies. The upgraded website comes as Americans begin to re-enter the workforce and businesses resume operations after closure and reduced production due to COVID-19. The website not only helps to attract out-of-state veterans to Indiana, but is uniquely positioned to help Hoosier veterans find their way back to work.Each year, hundreds of thousands of service members leave the military, with nearly half facing some period of unemployment. As the nation and State of Indiana continue re-opening, the national veteran unemployment rate stands at about 9 percent (as of May 2020), down from 11.8 percent in April, which was the highest unemployment rate for veterans since 2010. Meanwhile, there are more than 100,000 in-demand jobs available throughout IndianaThe centerpiece of the INvets program is a free interactive website for veterans that includes the most current information about job opportunities available in healthcare, logistics, manufacturing and tech, and other high-demand industries. More than a simple job board, INvets provides veterans details about the skills required for employment at each company and for each job, with links to education and training partners that offer the skills training, credentials or degrees needed. The website also provides information about communities across Indiana so veterans can explore all that Indiana has to offer.last_img read more

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Vikings vs. Patriots: Score, results, highlights from cross-conference battle

first_img4:34 p.m.: New England piling up the chunk plays early. Brady with completions for 24,18, 15, and 13 yards.4:27 p.m.: Minnesota will start with the ball and it gets an incomplete pass, short run from Dalvin Cook and a 6-yard completion that will force an early punt.3:36 p.m.: A couple of important Vikings players who have been battling injury will be active today.Stefon Diggs and Xavier Rhodes are active.— Adam Schefter (@AdamSchefter) December 2, 2018 Minnesota had the opportunity to get back in the game in the fourth quarter but Kirk Cousins threw an interception in the end zone which squashed any hope of a rally.Unlikely contributor James Develin, the rarely-used fullback, played a major role in the Patriots win, scoring his second and third touchdowns of the season on 1-yard rushes. New England’s offense was humming in the second half, but suffered in the first 30 minutes due some huge stops from the Vikings’ (6-5-1) defense that wound up keeping the score tight. Minnesota failed to capitalize on the Bears loss and stayed 1 1/2 games behind the Bears in the NFC North. Dalvin Cook ran for 84 yards on only nine carries, but the Vikings inability to throw the ball down the field prevented them from doing much on the offensive side of the ball. They will have a massively important matchup next week against the Seahawks, a fellow wild-card contender.MORE: Week 13 playoff picture | Week 13 updates, highlightsSporting News provided live updates from Vikings vs. Patriots. Vikings vs. Patriots: Score, results, highlights(All times ET)Vikings: 10Patriots: 24Final: Patriots 24, Vikings 107:21 p.m.: INTERCEPTION, PATRIOTS. The Vikings last-ditch attempt to score points is thwarted as Cousins is intercepted by Jonathan Jones. The Patriots will likely take a knee and run out the clock. 7:16 p.m.: New England has picked up a couple of first downs as we have hit the two-minute warning with the Patriots trying to run down the clock.7:07 p.m.: INTERCEPTION, PATRIOTS. Cousins takes a deep shot into the end zone but it’s underthrown and Duron Harmon comes up with a massive interception.🗣THIS INTERCEPTION WAS RIDICULOUS📺: FOX #GoPats pic.twitter.com/fchNF23VuT— NFL (@NFL) December 3, 20187:03 p.m.: INTERCEPTION, VIKINGS. We’re not done yet. Brady gets picked off by Eric Kendricks and the Vikings will get another chance to get within one [email protected] with the hit…and @EricKendricks54 with the pick!!! pic.twitter.com/0BZvmNBN4z— Minnesota Vikings (@Vikings) December 3, 20187:02 p.m.: Quick slant on a fourth-and-11 is the call by the Vikings but Laquon Treadwell is stopped well short and it’s a turnover on downs.6:53 p.m.: Controversial decision by the officials as Latavius Murray, who was stopped short on fourth-and-inches, is given a first down due to forward progress. Bill Belichick challenged but without definitive evidence the play stands.6:46 p.m.: TOUCHDOWN, PATRIOTS. James Develin pounds it in again for his second touchdown of the game and New England is up by two possessions. Patriots 24, Vikings 103 carries, 3 touchdowns this season.RT to send this guy back to the Pro Bowl.#ProBowlVote @James_Develin | #MINvsNE pic.twitter.com/E2SaZJixcL— New England Patriots (@Patriots) December 2, 20186:41 p.m.: A potential swing here as Cousins is sacked on a third down and Julian Edelman returns the ensuing punt to midfield.End of third quarter: Patriots 17, Vikings 106:33 p.m.: TOUCHDOWN, PATRIOTS. New England marches 75 yards on four plays, the biggest two of which were a pair of 24-yard completions to Josh Gordon, including a touchdown in the final minute of the third quarter. Patriots 17, Vikings 10Got ’em!TB12 to @JOSH_GORDONXII for the @Patriots TD!📺: FOX #GoPats pic.twitter.com/mleMHZ4Kkb— NFL (@NFL) December 2, 20186:28 p.m.: FIELD GOAL, VIKINGS. Bailey connects on a 39-yard field goal to tie the game, but the Vikings didn’t convert on two passes in the end zone during the drive and had to settle for three points. Vikings 10, Patriots 106:22 p.m.: A challenge by the Patriots and the referees to take a look at a close play on a Kyle Rudolph reception. Rudolph may have been short of the first down marker, but upon review, the call stands and it’s a Minnesota first down.6:15 p.m.: Gostkowski’s 48-yard field goal isn’t particularly close. Both teams have now missed field goal attempts in this game.6:12 p.m.: The Patriots opt for the aggressive choice on fourth-and-one and barely pick it up on a short pass from Brady to Chris Hogan.6:08 p.m.: Nothing doing for Minnesota either and Brady responds by coming out firing with a 29-yard completion to Cordarrelle Patterson5:58 p.m.: New England offense starts the second half with a three-and-out.Halftime: Patriots 10, Vikings 75:38 p.m.: TOUCHDOWN, VIKINGS. Adam Thielen finally makes his first catch of the day when he gets left wide open in the end zone. Vikings are on the board before the end of the half. Patriots 10, Vikings [email protected]’s first catch of the game could not have come at a better time.#ProBowlVote pic.twitter.com/9eO3C0aPa6— Minnesota Vikings (@Vikings) December 2, 20185:37 p.m.: A quartet of completions by Cousins has the Vikings inside the 10 and knocking on the door.5:30 p.m.: After Rob Gronkowski was stopped just short of the first down mark on a reception, the Vikings defense stuffs James White for a loss on third-and-inches and the Patriots will punt after the two-minute warning. 5:20 p.m.: No payoff for the Vikings after Cook’s run as the drive stalls. Diggs and Thielen have combined for one catch for six yards so far.5:17 p.m.: Cook’s strong start continues as he goes 18 yards on the first play of the Vikings’ drive.5:13 p.m.: FIELD GOAL, PATRIOTS. New England eats up a lot of clock, 8:11 to be exact, but can’t get in the end zone. Stephen Gostkowski kicks in a 20-yard field goal. A controversial third down no-call on a potential pass interference thwarted the Patriots’ touchdown aspirations. Patriots 10, Vikings 05:04 p.m.: Not a lot of variety recently for the Patriots, but it’s working. Brady with back-to-back dump offs to James White for double-digit yards.4:58 p.m.: The Vikings get their second three-and-out in three drives as their offense continues to struggle. End of first quarter: Patriots 7, Vikings 04:50 p.m.: A rare scramble to pick up a first down by Brady gives him another career milestone.5-yard gain.And that means…1,000 career rushing yards!👏👏👏 TB12!📺: FOX #GoPats #TB1K pic.twitter.com/jmqvuXbzur— NFL (@NFL) December 2, 20184:42 p.m.: Dan Bailey’s 48-yard field goal is shanked and not even close to going through the uprights. Minnesota comes up empty.4:39 p.m.: Dalvin Cook breaks a big run for the Vikings and goes 32 yards to the Patriots’ 23-yard line.4:34 p.m.: TOUCHDOWN, PATRIOTS. Fullback James Develin pounds it one yard up the middle for the touchdown. Early lead for New England. Patriots 7, Vikings 0. It wasn’t pretty, but the Patriots managed a 24-10 win over the Vikings to keep themselves in position for a first-round bye in the AFC.The defensive domination by New England (9-3) was close throughout much of the contest, but the Patriots broke a tie in the third quarter on a Josh Gordon touchdown, then added another score on their next drive and didn’t trail for the remainder of the game.last_img read more

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This protein designer aims to revolutionize medicines and materials

first_imgDavid Baker appreciates nature’s masterpieces. “This is my favorite spot,” says the Seattle native, admiring the views from a terrace at the University of Washington (UW) here. To the south rises Mount Rainier, a 4400-meter glacier-draped volcano; to the west, the white-capped Olympic Mountain range.But head inside to his lab and it’s quickly apparent that the computational biochemist is far from satisfied with what nature offers, at least when it comes to molecules. On a low-slung coffee table lie eight toy-sized, 3D-printed replicas of proteins. Some resemble rings and balls, others tubes and cages—and none existed before Baker and his colleagues designed and built them. Over the last several years, with a big assist from the genomics and computer revolutions, Baker’s team has all but solved one of the biggest challenges in modern science: figuring out how long strings of amino acids fold up into the 3D proteins that form the working machinery of life. Now, he and colleagues have taken this ability and turned it around to design and then synthesize unnatural proteins intended to act as everything from medicines to materials. Protein for every purposeThe ability to predict how an amino acid sequence will fold—and hence how the protein will function—opens the way to designing novel proteins that can catalyze specific chemical reactions or act as medicines or materials. Genes for these proteins can be synthesized and inserted into microbes, which build the proteins. Sander reasoned that the juxtaposition of those amino acids must be crucial to a protein’s function. If a mutation occurs, changing one of the amino acids so that it no longer interacts with its partner, the protein might no longer work, and the organism could suffer or die. But if both neighboring amino acids are mutated at the same time, they might continue to interact, and the protein might work as well or even better.The upshot, Sander proposed, was that certain pairs of amino acids necessary to a protein’s structure would likely evolve together. And researchers would be able to read out that history by comparing the DNA sequences of genes from closely related proteins in different organisms. Whenever such DNA revealed pairs of amino acids that appeared to evolve in lockstep, it would suggest that they were close neighbors in the folded protein. Put enough of those constraints on amino acid positions into an ab initio computer model, and the program might be able to work out a protein’s full 3D structure.Unfortunately, Sander says, his idea “was a little ahead of its time.” In the 1990s, there weren’t enough high-quality DNA sequence data from enough similar proteins to track coevolving amino acids.By the early part of this decade, however, DNA sequences were flooding in thanks to new gene-sequencing technology. Sander had also teamed up with Debora Marks at Harvard Medical School in Boston to devise a statistical algorithm capable of teasing out real coevolving pairs from the false positives that plagued early efforts. In a 2011 article in PLOS ONE, Sander, Marks, and colleagues reported that the coevolution technique could constrain the position of dozens of pairs of amino acids in 15 proteins—each from a different structural family—and work out their structures. Since then, Sander and Marks have shown that they can decipher the structure of a wide variety of proteins for which there are no homology templates. “It has changed the protein-folding game,” Sander says.I have been waiting 10 years for a breakthrough. This seems to me a breakthrough.John Moult, University of Maryland, College ParkIt certainly did so for Baker. When he and colleagues realized that scanning genomes offered new constraints for Rosetta’s ab initio calculations, they seized the opportunity. They were already incorporating constraints from NMR and other techniques. So they rushed to write a new software program, called Gremlin, to automatically compare gene sequences and come up with all the likely coevolving amino acid pairs. “It was a natural for us to put them into Rosetta,” Baker says.The results have been powerful. Rosetta was already widely considered the best ab initio model. Two years ago, Baker and colleagues used their combined approach for the first time in an international protein-folding competition, the 11th Critical Assessment of protein Structure Prediction (CASP). The contest asks modelers to compute the structures of a suite of proteins for which experimental structures are just being worked out by x-ray crystallography or NMR. After modelers submit their predictions, CASP’s organizers then reveal the actual experimental structures. One submission from Baker’s team, on a large protein known as T0806, came back nearly identical to the experimental structure. Moult, who heads CASP, says the judge who reviewed the predicted structure immediately fired off an email to him saying “either someone solved the protein-folding problem, or cheated.”“We didn’t [cheat],” Sergey Ovchinnikov, a grad student in Baker’s lab, says with a chuckle.The implications are profound. Five years ago, ab initio models had determined structures for just 56 proteins of the estimated 8000 protein families for which there is no template. Since then, Baker’s team alone has added 900 and counting, and Marks believes the approach will already work for 4700 families. With genome sequence data now pouring into scientific databases, it will likely only be a couple years before protein-folding models have enough coevolution data to solve structures for nearly any protein, Baker and Sander predict. Moult agrees. “I have been waiting 10 years for a breakthrough,” he says. “This seems to me a breakthrough.”For Baker, it’s only the beginning. With Rosetta’s steadily improving algorithms and ever-greater computing power, his team has in essence mastered the rules for folding—and they’ve begun to use that understanding to try to one-up nature’s creations. “Almost everything in biomedicine could be impacted by an ability to build better proteins,” says Harvard synthetic biologist George Church. Information can be coded into protein sequences, like DNA. V. Altounian/Science Video of Protein Folding Click to view the privacy policy. Required fields are indicated by an asterisk (*) In a protein-folding competition, Baker’s team stunned judges by almost matching the actual structure. Channels through membranes act as gateways. From DNA to proteinsThe machinery for building proteins is essential for all life on earth. Click on the arrows at the bottom or swipe horizontally to learn more. From DNA to proteinsThe machinery for building proteins is essential for all life on earth.Building proteins begins with DNA’s genetic code.In protein-coding regions of genes, each amino acid is encoded by three rungs of the DNA ladder. Twenty such amino acids make up the building blocks of proteins.Double stranded DNA is transcribed into single-stranded RNA, which is then sent to the ribosome where proteins are manufactured.A molecular machine called the ribosome translates each RNA coding sequence into an amino acid, building up a growing protein chain.Forces between amino acids cause a linear chain to fold up on itself, creating a functional 3D protein.‹›One way around the problem is to determine protein structures experimentally, through methods such as x-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. But that’s slow and expensive. Even today, the Protein Data Bank, an international repository, holds the structures of only roughly 110,000 proteins out of the hundreds of millions or more thought to exist.Knowing the 3D structures of those other proteins would offer biochemists vital insights into each molecule’s function, such as whether it serves to ferry ions across a cell membrane or catalyze a chemical reaction. It would also give chemists valuable clues to designing new medicines. So, instead of waiting for the experimentalists, computer modelers such as Baker have tackled the folding problem with computer models.They’ve come up with two broad kinds of folding models. So-called homology models compare the amino acid sequence of a target protein with that of a template—a protein with a similar sequence and a known 3D structure. The models adjust their prediction for the target’s shape based on the differences between its amino acid sequence and that of the template. But there’s a major drawback: There simply aren’t enough proteins with known structures to provide templates—despite costly efforts to perform industrial-scale x-ray crystallography and NMR spectroscopy. Templates were even scarcer more than 2 decades ago, when Baker accepted his first faculty position at UW. That prompted him to pursue a second path, known as ab initio modeling, which calculates the push and pull between neighboring amino acids to predict a structure. Baker also set up a biochemistry lab to study amino acid interactions, in order to improve his models.Early on, Baker and Kim Simons, one of his first students, created an ab initio folding program called Rosetta, which broke new ground by scanning a target protein for short amino acid stretches that typically fold in known patterns and using that information to help pin down the molecule’s overall 3D configuration. Rosetta required such extensive computations that Baker’s team quickly found themselves outgrowing their computer resources at UW.Seeking more computing power, they created a crowdsourcing extension called [email protected], which allows people to contribute idle computer time to crunching the calculations needed to survey all the likely protein folds. Later, they added a video game extension called Foldit, allowing remote users to apply their instinctive protein-folding insights to guide Rosetta’s search. The approach has spawned an international community of more than 1 million users and nearly two dozen related software packages that do everything from designing novel proteins to predicting the way proteins interact with DNA.“The most brilliant thing David has done is build a community,” says Neil King, a former Baker postdoc, now an investigator at UW’s Institute for Protein Design (IPD). Some 400 active scientists continually update and improve the Rosetta software. The program is free for academics and nonprofit users, but there’s a $35,000 fee for companies. Proceeds are plowed back into research and an annual party called RosettaCon in Leavenworth, Washington, where attendees mix mountain hikes and scientific talks.Despite this success, Rosetta was limited. The software was often accurate at predicting structures for small proteins, fewer than 100 amino acids in length. Yet, like other ab initio programs, it struggled with larger proteins. Several years ago, Baker began to doubt that he or anyone else would ever manage to solve most protein structures. “I wasn’t sure whether I would get there.”Now, he says, “I don’t feel that way anymore.”What changed his outlook was a technique first proposed in the 1990s by computational biologist Chris Sander, then with the European Molecular Biology Laboratory in Heidelberg, Germany, and now with Harvard. Those were the early days of whole genome sequencing, when biologists were beginning to decipher the entire DNA sequences of microbes and other organisms. Sander and others wondered whether gene sequences could help identify pairs of amino acids that, although distant from each other on the unfolded proteins, have to wind up next to each other after the protein folds into its 3D structure.Clues from genome sequencesComparing the DNA of similar proteins from different organisms shows that certain pairs of amino acids evolve in tandem—when one changes, so does the other. This suggests they are neighbors in the folded protein, a clue for predicting structure.  Baker’s lab is abuzz with other projects. Last year, his group and collaborators reported engineering into bacteria a completely new metabolic pathway, complete with a designer protein that enabled the microbes to convert atmospheric carbon dioxide into fuels and chemicals. Two years ago, they unveiled in Science proteins that spontaneously arrange themselves in a flat layer, like interlocking tiles on a bathroom floor. Such surfaces may lead to novel types of solar cells and electronic devices.In perhaps the most thought-provoking project, Baker’s team has designed proteins to carry information, imitating the way DNA’s four nucleic acid letters bind and entwine in the genetic molecule’s famed double helix. For now, these protein helixes can’t convey genetic information that cells can read. But they symbolize something profound: Protein designers have shed nature’s constraints and are now only limited by their imagination. “We can now build a whole new world of functional proteins,” Baker says. V. Altounian/Science center_img Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Baker notes that for decades researchers pursued a strategy he refers to as “Neandertal protein design,” tweaking the genes for existing proteins to get them to do new things. “We were limited by what existed in nature. … We can now short-cut evolution and design proteins to solve modern-day problems.”Take medicines, such as drugs to combat the influenza virus. Flu viruses come in many strains that mutate rapidly, which makes it difficult to find molecules that can knock them all out. But every strain contains a protein called hemagglutinin that helps it invade host cells, and a portion of the molecule, known as the stem, remains similar across many strains. Earlier this year, Baker teamed up with researchers at the Scripps Research Institute in San Diego, California, and elsewhere to develop a novel protein that would bind to the hemagglutinin stem and thereby prevent the virus from invading cells.The effort required 80 rounds of designing the protein, engineering microbes to make it, testing it in the lab, and reworking the structure. But in the 4 February issue of PLOS ONE, the researchers reported that when they administered their final creation to mice and then injected them with a normally lethal dose of flu virus, the rodents were protected. “It’s more effective than 10 times the dose of Tamiflu,” an antiviral drug currently on the market, says Aaron Chevalier, a former Baker Ph.D. student who now works at a Seattle biotech company called Virvio here that is working to commercialize the protein as a universal antiflu drug.Another potential addition to the medicine cabinet: a designer protein that chops up gluten, the infamous substance in wheat and other grains that people with Celiac disease or gluten sensitivity have trouble digesting. Ingrid Swanson Pultz began crafting the gluten-breaker even before joining Baker’s lab as a postdoc and is now testing it in animals and working with IPD to commercialize the research. And those self-assembling cages that debut this week could one day be filled with drugs or therapeutic snippets of DNA or RNA that can be delivered to disease sites throughout the body.The potential of these unnatural proteins isn’t limited to medicines. Baker, King, and their colleagues have also attached up to 120 copies of a molecule called green fluorescent protein to the new cages, creating nano-lanterns that could aid research by lighting up as they move through tissues.Church says he believes that designer proteins might soon rewrite the biology inside cells. In a paper last year in eLife, he, Baker, and colleagues designed proteins to bind to either a hormone or a heart disease drug inside cells, and then regulate the activity of a DNA-cutting enzyme, Cas9, that is part of the popular CRISPR genome-editing system. “The ability to design sensors [inside cells] is going to be big,” Church says. The strategy could allow researchers or physicians to target the powerful gene-editing system to a specific set of cells—those that are responding to a hormone or drug. Biosensors could also make it possible to switch on the expression of specific genes as needed to break down toxins or alert the immune cells to invaders or cancer. Sensors travel throughout the body to detect various signals. 2D arrays can be used as nanomaterials in various applications. Sign up for our daily newsletter Get more great content like this delivered right to you! Country Email V. Altounian/Science If the ability to read and write DNA spawned the revolution of molecular biology, the ability to design novel proteins could transform just about everything else. “Nobody knows the implications,” because it has the potential to impact dozens of different disciplines, says John Moult, a protein-folding expert at the University of Maryland, College Park. “It’s going to be totally revolutionary.”Baker is by no means alone in this pursuit. Efforts to predict how proteins fold, and use that information to fashion novel versions, date back decades. But today he leads the charge. “David has really inspired the field,” says Guy Montelione, a protein structure expert at Rutgers University, New Brunswick, in New Jersey. “That’s what a great scientist does.”Baker, 53, didn’t start out with any such vision. Though both his parents were professors at UW—in physics and atmospheric sciences—Baker says he wasn’t drawn to science growing up. As an undergraduate at Harvard University, Baker tried studying philosophy and social studies. That was “a total waste of time,” he says now. “It was a lot of talk that didn’t necessarily add content.” Biology, where new insights can be tested and verified or discarded, drew him instead, and he pursued a Ph.D. in biochemistry. During a postdoc at the University of California, San Francisco, when he was studying how proteins move inside cells, Baker found himself captivated instead by the puzzle of how they fold. “I liked it because it’s getting at something fundamental.”In the early 1960s, biochemists at the U.S. National Institutes of Health (NIH) recognized that each protein folds itself into an intrinsic shape. Heat a protein in a solution and its 3D structure will generally unravel. But the NIH group noticed that the proteins they tested refold themselves as soon as they cool, implying that their structure stems from the interactions between different amino acids, rather than from some independent molecular folding machine inside cells. If researchers could determine the strength of all those interactions, they might be able to calculate how any amino acid sequence would assume its final shape. The protein-folding problem was born. Science Cages can contain medicinal cargo or carry it on their surfaces. Already, this virtuoso proteinmaking has yielded an experimental HIV vaccine, novel proteins that aim to combat all strains of the influenza viruses simultaneously, carrier molecules that can ferry reprogrammed DNA into cells, and new enzymes that help microbes suck carbon dioxide out of the atmosphere and convert it into useful chemicals. Baker’s team and collaborators report making cages that assemble themselves from as many as 120 designer proteins, which could open the door to a new generation of molecular machines. Antagonists bind to a target protein, blocking its activation.last_img read more

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