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Immunology: The Powers of Proteins
What is Immunology?
Immunology, a large branch of medical science, studies all aspects of the immune system and how it functions, in both illness and health. Immunologists look at physical, chemical, and physiological components of the immune system. Its main organs—including bone marrow, thymus gland, tonsils, and skin—are designed to protect our bodies from potentially harmful infections. When the immune system functions incorrectly, a wide range of problems, from arthritis to chronic infections, can result. The earliest written mention of immunology was during the Plague of Athens in 430 BCE.
Irene Maier’s first big project in immunology brought her a Ph.D. in biochemistry at the University of Vienna. Funded in part through a UNESCO-L’Oréal Fellowship, she worked on developing a biochip that could help diagnose food allergies. An allergy is caused by an overactive immune system. If a person has an allergy to something that’s usually harmless—like peanuts—the immune system will overreact and quickly attack that substance. This is what causes the itchy eyes and runny nose of an allergic reaction. By using Irene’s diagnostic chip, a doctor could identify the cause of a food allergy, and advise the patient to stay away from whichever food was causing all those symptoms.
Now, she has become a structural biologist on a postdoctoral fellowship at California Institute of Technology (Caltech). “I specialize in computational protein design, using computers to predict how the function of a protein might be altered when you change the sequence of its constituent amino acids,” she explains. Her experiments are testing whether redesigning a protein’s structure in the lab can help control the way the immune system responds to a foreign substance.
After recognizing her growing interest in how proteins interact, she approached professor Steve Mayo, an expert in protein design at Caltech, and asked if she could join his lab to learn more about their techniques. When Professor Mayo agreed to sponsor her, a delighted Irene moved from Austria to southern California in 2009.
She loves the challenge of trying to master a new technique. “I like to go into structures and learn more about how they interact. In trying to put my ideas into the real world, I have a lot of flexibility. As long as it fits in with the current project, we’re allowed to do a lot of things. It’s up to me to decide how I want to reach the goal.”
Scientists can use the lab whenever they want. Irene appreciates the flexible hours. “It’s a creative job, and I’m often most productive late at night,” she notes. “If all the work isn’t done between Monday and Friday, or I just want to finish something, I come in on a weekend. You can often plan experiments so you don’t have to be there on Sunday night, but with continuous experiments, you sometimes need to visit the lab for an hour.”
Managing all that flexibility is a challenge. Irene feels pressure to get things done, on top of the frustration when experiments don’t work. “You have to stay motivated when you’re repeating an experiment again and again—eventually it will work.”
Irene enjoys human interactions as much as structural ones. She says she loved teaching undergraduate biochemistry at the University of Vienna, as well as collaborating with other scientists in different fields and getting great input. “I’m in contact with people from all over the world,” she enthuses.
Even when the work is difficult, Irene’s enthusiasm persists. “I want to get it done! If I don’t know how it works, I want to find out.”
Solving One of Life’s Puzzles
Joan Steitz concurs. ”Science is all about discovery,” exclaims the Yale University Sterling Professor of Molecular Biophysics and Biochemistry and Howard Hughes Medical Institute Investigator. “A wonderful thing about a university, with students to teach or work with in your lab, is that they get excited about discoveries. You’re sharing the joy with them. It’s really neat!” she says. “Sometimes you’re doing an experiment, get a new piece of data, look at it and say, ‘That’s the answer!’ And you’re the only person on Earth who knows that,” she recounts. “You can hardly wait to share it with others in the lab, and then with more people by publishing.”
Joan, who is a 2001 L’Oréal-UNESCO Award winner, discovered and defined the function of mammalian cells called small nuclear ribonucleoproteins (snRNPs), which retrieve the important genetic information from DNA, where it is interspersed with what she calls ‘junk.’ “snRNPs are the machinery that gets rid of the junk and splices together the useful information. Then ribosomes can make proteins without interference from the junky stuff,” she explains. Her initial hypothesis and basic findings took two years. Then 10 other labs spent five more years to further explore, confirm, and understand snRNPs.
During her research, Joan remembers testing a particular hypothesis, trying to find the beginning of the gene that will eventually make the right protein. “I developed the film and could see—for the first time—exactly HOW they do it! I drove home at 2 a.m. thinking, ‘Every cell in my body is doing that right now.’”
Joan’s groundbreaking research of that mysterious splicing process has been important for understanding how proteins are formed. This is especially important for immunology research, since it is this kind of splicing that creates all the different types of antibodies that can recognize and defend the body against the millions of viruses and bacteria out there. It’s also allowed her to explore other biological processes, including the intricate changes that occur as the immune system and the brain develop. Now, Joan and other scientists are hoping that her research can help lead to new treatments for all sorts of serious immune system disorders.
As a lab manager, she misses doing hands-on research, but believes it’s vital to teach and train the next generation of scientists. “Groups working at different levels in your lab increases the reward level, with more people sharing discoveries, visions, and questions with you. It does get hectic, though,” Joan acknowledges. She’s eager to reach her lab each day “to learn what’s new, and share the enthusiasm of the people actually producing the results.” She works with seven postdoctoral fellows, five undergraduates, several advanced scientists, and some graduate students.
Don’t let hard work or long hours scare you, advises Joan, who often spends nine hours a day in her lab. “You put them in not because anyone says you have to, but because you want to. You’re so curious about what’s going on, you want to get answers more quickly.” Scientists typically set their own hours, which change with a project’s stage.
For Joan, the fun’s always the excitement of “finding out how things work inside living organisms. That’s what it’s all about!”
Looking for the “Little Things”
Philippa Marrack, too, “loves finding answers to life’s puzzles.” The University of Colorado immunology Professor is proud that her team solved “one of the ways the immune system knows not to attack the person it lives inside of. It was really fun to figure that out. Now the world understands better how life’s machinery operates.”
Philippa studies survival and function of T cells, of which everyone has about a million million. Each T cell has 40,000 unique protein “receptors” on its surface, different from every other T cell’s receptors. Any infectious organism also has proteins on its surface—called antigens—some of which may randomly match a particular T cell’s receptor. When antigen and receptor come together, the T cell is alerted and multiplies rapidly to attack the invading germ. Philippa’s lab discovered what the T cell protein receptors look like, so they can be identified and studied.
Most scientists are driven by wanting to unravel mysteries, but “you have to delight in little things along the way,” says Philippa, a Howard Hughes Medical Institute Scholar and L’Oréal-UNESCO Award winner in 2004. “It’s a mistake to think that scientists lead solitary existences. Immunologists interact with people all the time. We educate, learn, discuss, and depend on our colleagues for ideas.”
Her biggest challenge was integrating science and family, trying to care for two (now grown) children as well as her aging parents. Taking time off can be challenging, because when you’re not in the lab, you’re not producing or publishing data. “And the more successful you are, the more people you’re responsible for,” Philippa reflects. She has found a way to balance her family needs with those of her lab and career. “Somehow, you reach an equilibrium.”
Philippa and her husband, John Kappler, jointly run their lab, supervising over 20 people. “In 36 years of marriage, the only thing that’s always gone smoothly was doing science together,” she confides. “We were both trained as chemists—important for understanding biology, because our bodies are made of chemicals—but have different skills in the kind of science we each understand or manage best. He’s very careful and precise. I’ll do the faster experiments, where cells would die quickly. People get joy from the things they’re good at.” Together they make a great team, like receptors and antigens.