In the summer of 1989, nine-year-old Ahmad \u201cMo\u201d Khalil<\/a> immigrated with his family to America from Riyadh, Saudi Arabia. As their plane descended into JFK Airport, Khalil and his younger brother Ayman pressed their faces against the window. They recognized the Manhattan skyline from movies and were slightly chagrined not to see Superman buzz past the Statue of Liberty. Other than Superman\u2019s absence, there weren\u2019t many other moments of cultural dismay for the Khalil boys, who otherwise adapted quickly to their adopted country.<\/p>\n \u201cMy brother and I were young and malleable,\u201d says Khalil, now an assistant professor of biomedical engineering<\/a> at Boston University. The two boys also had plenty of practice adjusting to new places. Prior to Riyadh, they had lived in Jordan, Dubai, and Greece, thanks to their father\u2019s career as a globetrotting pharmaceutical sales executive. Along the way, the Khalil boys had attended international schools, learned English, and sampled the cuisine of many nations at their dinner table. And their new home in northern New Jersey (where a third brother, Karim, would be born) was well within the multicultural orbit of New York City.<\/p>\n But Khalil says his real key to acceptance by his American peers was sports. He played baseball and excelled at soccer for both club and school teams all the way through college at (nationally ranked) Stanford. That team orientation continues to serve him well today in the decidedly cross-disciplinary field of synthetic biology. Indeed, collaboration is at the heart of Boston University\u2019s recently launched Biological Design Center (BDC)<\/a>, where Khalil is the associate director.<\/p>\n <\/p>\n Synthetic biology\u2014or engineering biology, as it is sometimes called\u2014offers immense promise, from growing organs for transplant to reengineering immune cells to kill cancer. But the field is very young, still in what Khalil likes to call the \u201ctinkering\u201d phase. The mission of the BDC, which will soon occupy the fourth and fifth floors of BU\u2019s new Center for Integrated Life Sciences & Engineering<\/a> building, is to bring together scientists who can \u201ctinker\u201d at every level of this ambitious enterprise\u2014from genetic switches to cellular functions to multicellular systems\u2014in the hope of building on one another\u2019s discoveries.<\/p>\n<\/div>\n More mature fields of engineering have developed reliable tools that can be used to create more complex devices, Khalil says. \u201cFor example, if I\u2019m an electrical engineer and I want to build a computer, I don\u2019t need to work at the level of designing my own transistor.\u201d To reach that advanced stage in synthetic biology, \u201cthere needs to be time for tinkering,\u201d Khalil says. \u201cThere needs to be time to play with as many of the biological components and bio-circuitry out there, to learn from them and what they can do.\u201c<\/p>\n The mission of the [Biological Design Center]\u2026is to bring together scientists who can \u201ctinker\u201d at every level\u2026in the hope of building on one another\u2019s discoveries.<\/p><\/blockquote>\n Khalil, 36, has an infectious enthusiasm for synthetic biology, even the simplified version he doles out during a recent interview in his office. Wearing a tan, herringbone jacket, a checked shirt, and jeans on his wiry frame, he gesticulates and punctuates answers with exclamations like, \u201cRight!\u201d and \u201cOh yeah!\u201d<\/p>\n At one point, Khalil waves toward a sleek espresso maker by his desk. It\u2019s a multi-knobbed contraption of chrome and brushed nickel, complete with a glass warmer, milk frother, and magnetic stirrer.<\/p>\n \u201cI use it to lure postdocs and grad students or anybody with an idea or data they want to show me, with an offer of free coffee,\u201d he says. It\u2019s a small gesture, but telling: Khalil is proactive about sharing knowledge and collaborating.<\/p>\n \u201cMo is one of those people whose first instinct is to say, \u2018yes, let\u2019s try it,\u2019 as opposed to saying, \u2018no, this is too complicated,\u2019\u201d says fellow BDC researcher Douglas Densmore<\/a>, an associate professor of electrical and computer engineering<\/a> who develops software to automate the creation of synthetic DNA and RNA molecules.<\/p>\n According to the BDC\u2019s director, Christopher Chen<\/a>, a professor of biomedical engineering, \u201cnot only does [Khalil] do his own exciting science, he also makes the people around him more energized about what they\u2019re doing. He finds links between his work and a wide range of others\u2019 interests, including mine.\u201d<\/p>\n Chen points out that while the new lab space will be a focal point for engineering biology at BU, \u201cthe BDC is bigger than this new building,\u201d and not every investigator working with the BDC will be moving within its walls.<\/p>\n As Khalil tells it, the seed idea for the BDC was planted during a lunch of pasta and panini at Scoozi in nearby Kenmore Square that he and other junior faculty had with the more senior Chen when the latter was being recruited by BU in 2013. At the time, the University\u2019s synthetic biology efforts were anchored by Jim Collins<\/a>, a pioneer in the field. In addition to Collins, who would leave for MIT in 2014, there was a nucleus of young, recently hired researchers who now form the core faculty of the BDC, including Khalil, Densmore, and Wilson Wong<\/a>, an assistant professor of biomedical engineering.<\/p>\n \u201cAt that lunch, there was this new crew of people talking with Chris, a legend in the field of mechanobiology and tissue engineering,\u201d Khalil says. \u201cThere was an \u2018aha\u2019 moment, when we realized that we were all thinking about similar ways to tackle very different problems.\u201d<\/p>\n One way to phrase the shared approach: learning by building. For instance, you can learn a lot about how cells turn certain genes on and off by designing and testing different proteins known as \u201ctranscription factors,\u201d that work like genetic switches. Once a biological mechanism can be built, it can be tweaked and eventually harnessed to help solve problems such as fighting disease and creating new energy sources.<\/p>\n Synthetic biology isn\u2019t about using the building blocks of life to create something entirely new from scratch, says Khalil. It\u2019s about employing the amazing powers that nature has evolved over billions of years. \u201cWe can tap into the fact that our immune cells are basically heat-seeking missiles for tumors, or the fact that plants can harness energy from the sun,\u201d he says. \u201cLet\u2019s build on those evolved schemes and rewire them, because that\u2019s where we\u2019ll make the most impact.\u201d<\/p>\n Once a biological mechanism can be built, it can be tweaked and eventually harnessed to help solve problems such as fighting disease and creating new energy sources.<\/p><\/blockquote>\n For example, Wong\u2019s lab is engineering immune cells, which are infused into cancer patients, to boost their safety and tumor-killing potency. Chen is investigating how best to create the blood vessels needed for synthetic heart and other tissue. And Khalil is making new RNA molecules (which carry DNA\u2019s protein-making instructions) that can be used to help doctors quickly diagnose an antibiotic-resistant infection.<\/p>\n Khalil\u2019s antibiotic-resistance research began when he was a postdoc with Collins, whose lab is a collaborator on the current project. The problem it confronts is huge. Due partly to the overuse of antibiotics, dangerous bacteria are mutating into drug-resistant strains at an accelerating rate that far outpaces the development of new drugs<\/a>. Currently, it can take two to three days to test whether an infection is drug resistant, because the bacteria must be cultured and then hit with antibiotics to see what happens. Khalil and his team hope to cut that time down to a few hours by detecting bacteria\u2019s initial genetic reactions to a drug, allowing a more precise and effective treatment. They will create a diagnostic tool with RNA engineered to produce a colorimetric or fluorescent signal if they encounter partner RNAs created by bacteria reacting to a drug.<\/p>\n There are different types of RNA that must interact in the chain of events that lead from the genetic code of DNA to the genetic expression of protein creation inside cells. Think of the synthetic RNA as genetic switches that only turn on when they bind with RNA that bacteria generate during a genetic response to an antibiotic attack. The first step in creating these switches is finding the precise sequences of RNA you\u2019re targeting through a painstaking study of genetic reactions to different antibiotics by both drug-resistant and drug-susceptible bacteria.<\/p>\n \u201cFor some bacteria-drug combinations, we have a first set of genetic signatures,\u201d Khalil says. \u201cBut for the larger set, it\u2019s unknown.\u201d<\/p>\n Much of this work is being done in the lab of a collaborator on the project, Caroline Genco<\/a>, professor of integrative physiology and pathobiology at Tufts University<\/a>. In early 2017, one of Khalil\u2019s graduate students began working part time in Genco\u2019s lab, which studies the bacteria being used to develop the sensor\u2014a multi-drug-resistant strain of gonorrhea that the Centers for Disease Control and Prevention puts in the highest level of threats to public health and drug-resistant infections. This is where the talk of collaboration turns into action, says Genco.<\/p>\n \u201cCollaboration isn\u2019t just about Mo and me talking and writing a research proposal,\u201d she says. \u201cYou need a person who can bridge both worlds and will do the actual work.\u201d<\/p>\n After the researchers know what RNAs they are targeting, the next step is to design and synthesize the RNA switches that will bind to those targets and, in turn, trigger the fluorescence that will show up on the sensor. This is another big challenge, because there\u2019s not just one RNA sequence that could possibly act as a switch, but several, which vary greatly in reliability. The process of finding the best option starts with computer modeling of candidate RNAs, Khalil explains, \u201cand from there we synthesize the RNAs, put them into reactions, and screen them to see which give the best on and off properties.\u201d<\/p>\n <\/p>\n Synthesized RNA is made from a template of synthesized DNA, and in Khalil\u2019s lab that process begins with Federal Express. Specifically, they order DNA strands from a biotech company that ships the genetic strands overnight. Khalil\u2019s lab then uses custom-made enzymes to cut and paste the DNA into a new sequence. Next, they make a bunch of copies of the new DNA by putting it into a fast-multiplying organism such as E. coli<\/em>. Finally, they isolate the DNA and sequence it so it can be checked for errors.<\/p>\n<\/div>\n Ultimately, the researchers will create several RNA switches, each linked to a different drug on the menu of antibiotics a doctor might use to treat a patient. They will incorporate these switches into a diagnostic tool that can give doctors a color-coded assessment of an infection\u2019s drug susceptibility within minutes.<\/p>\n While the longer-term tests of antibiotics using cultured bacteria will likely remain the gold standard for identifying drug resistance, Khalil says there\u2019s a dire need for a faster diagnostic tool so that doctors can make a reasonably informed choice of prescription before their patients leave the hospital or clinic.<\/p>\n \u201cWhat\u2019s currently done is that a doctor makes a decision based on symptoms and relies on broad-spectrum antibiotics,\u201d says Khalil, meaning the subset of antibiotics known to be effective on the broadest range of infections. \u201cThose are generally effective, but not specific, so you\u2019re fueling resistance.\u201d<\/p>\n <\/p>\n The most prominent decorations in Khalil\u2019s office are the poster-sized prints of covers from journals in which he and his lab team have published, including a few designed by Khalil\u2019s wife, Katie Flynn, a Boston architect. \u201cShe\u2019s a reluctant cover artist,\u201d Khalil notes. \u201cShe does it for me.\u201d<\/p>\n The couple met at Stanford, where they lived in the same sophomore dorm and took a few of the same classes. Flynn majored in art, which had been one of Khalil\u2019s abiding interests growing up, along with architecture. One of his watercolors, painted as a teenager while visiting family in Jordan, hangs in their dining room. It depicts a couple sitting in the desert and gazing down into a valley at the Sea of Galilee.<\/p>\n \u201cI suspect what motivated him as a painter was precision,\u201d she says. \u201cHe loves drafting. He likes getting the drawings just right. That painting is really precise.\u201d<\/p>\n Both of Khalil\u2019s brothers describe him as \u201cwell-rounded,\u201d but not in the dabbling sense. When Khalil painted, he won awards. When he played sports, his teams won state championships. In high school, he was the valedictorian.<\/p>\n \u201cMo has this unique ability to go super-deep in a lot of different fields,\u201d says their middle brother, Ayman, who manages a data analytics team for Apple. \u201cHe can sit down, hit the books, and memorize something, and at the same time, sit back and think abstractly and big-picture.\u201d<\/p>\n Their youngest brother, Karim, who is now a mechanical engineering doctoral student at MIT, suspects that Khalil felt some pressure to succeed as the oldest son of immigrant parents. \u201cThey were willing to move across the world, to the United States, away from their family in the Middle East, to provide opportunities for success for their children,\u201d he says. \u201cI think that led Mo to want to be the best he could be, in everything.\u201d<\/p>\n By the time Khalil enrolled at Stanford, his desire to make art had waned. Instead, he combined that interest in design with his talent for math and science and majored in mechanical engineering with dreams of building rockets. As an undergraduate, he interned at NASA\u2019s Ames Research Center<\/a>, and in his senior year, he was actively networking for a job at the Jet Propulsion Laboratory<\/a>. That same year, however, he took a course that changed his trajectory.<\/p>\n The course, taught by a biomechanical engineer named Charles Taylor, focused on studying the cardiovascular system using the tools of engineering, such as modeling the fluid dynamics of blood flow.<\/p>\n \u201cWhat I previously knew of biology was shaped by how it\u2019s canonically taught, which often relies on memorization of proteins and pathways,\u201d Khalil says. \u201cBut [Taylor] showed how you can take a complex biological system and understand it in terms of general functioning, so you can study it quantitatively and rationally, and that\u2019s something engineers do really well.\u201d<\/p>\n It was also personal to Khalil. When he was in high school, his dad endured emergency double bypass surgery, and Khalil was amazed to learn how Taylor could use simulations of blood flow on a computer to diagnose cardiovascular disease.<\/p>\n \u201cHe said, \u2018this is a really exciting field with a lot of room for creativity and a lot of open-ended questions,\u2019\u201d Khalil recalls. Taylor advised him to apply to MIT for graduate school to pursue this new approach to biology, which he did. Two years after Khalil moved to Cambridge, Flynn enrolled at MIT too, for architecture. They married seven years later and now have two daughters, ages five and three.<\/p>\n![\"16-10359-OFFICEMO-035\"](\"\/eng\/files\/2022\/09\/Khalil_Aside1@2x.jpg\")
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