College: City College
Awards: National Science Foundation Graduate Research Fellowship, 2012
Unraveling the Mysteries of TB
Jemila Caplan Kester (City College, BS in biology, summa cum laude 2010) enrolled at Harvard University's School of Public Health hoping to accomplish two things: "First, to work on a globally relevant pathogen and, second, to do really cool biology."
Reaching those twin goals - with tuberculosis in her sights - has become easier, thanks to a 2012 National Science Foundation Graduate Research Fellowship. This is the most prestigious award a graduate student in the STEM disciplines (science, technology, engineering and mathematics) can receive. Providing $126,000 over three years, it recognizes and supports exceptional students who have proposed graduate-level research projects in their fields.
Kester is intrigued by the astounding estimate that a third of the world's population is infected with latent tuberculosis, which is caused by the bacterium Mycobacterium tuberculosis."They're infected, but they're not sick. At any time, the disease could be reactivated, and they could become sick and contagious," she says.
"My project is to understand how two people can be infected with TB - one dies and one lives with it for 50 years and never gets sick or gives it to anyone else. I'm looking at this diversity from the single-cell level, to try to see why two bacteria, which technically are genetically identical, don't behave the same."
The bacterium that causes human tuberculosis is part of a large family called Mycobacteria. Mycobacterial cells have poles - Kester likens it to a banana having one end with a stem and one end without - and when they divide, the new cell grows from one pole and not the other. If division is asymmetric, the materials in the mother cells are not equally distributed to the daughters; proteins, membrane compartments and other components can be differentially distributed. This results in variation among individuals (the phenotype) that is not related to DNA (the genotype). In this way, a clonal population of nearly identical cells could become phenotypically diverse, creating different disease states between people - and even within the same person.
But what's the mechanism that makes asymmetry occur? She thought that a key might lie in the work of Lucy Shapiro (Brooklyn College, AB cum laude, 1962), a Stanford University professor of developmental biology and director of Stanford's Beckman Center for Molecular and Genetic Medicine. "Her work on how a different bacterium establishes asymmetry pointed me in the direction of Clp protease, an enzyme that chews up other proteins involved in establishing polarity. I thought, ‘Maybe Clp is involved here, too.' And it was!"
Now in her first year at Harvard, she's working in the laboratory of Sarah Fortune, who looks at how M. tuberculosis uses specialized secretion systems and surface structures to mediate interactions with the infected host.
Kester is studying certain proteins of a nonpathogenic relative of TB that behaves similarly to the infectious one but grows faster. She tinkers with substances in the cells, adding things or subtracting them. "I make movies of my cells to see what happens and do a lot of quantitative microscopy of single cells," she says.
She says there's more to her research than the search for knowledge. "I really care about lessening disparities between the more economically privileged countries in the West and those in the Third World and even within our own country. Living in New York City for 11 years, I saw differences between affluent and poor areas. I worked in a Harlem drug rehab program and at a top Midtown company - the whole spectrum. I want to know my research will impact the world."
When she studied at City College, Kester earned several honors. A National Institutes of Health Minority Access to Research Careers (MARC) Fellowship paid for a stipend, tuition and other costs. "You're working in a lab and don't have to have another job to support yourself," she says. "I consider myself a typical CCNY student. I don't think I knew anybody there where money wasn't a problem. The MARC Fellowship relieved that pressure. You can concentrate on your research, and that's what gets you into Harvard."
Kester was selected as the 2006-07 Sharon Cosloy Scholar for her research with biology Professor Shubha Govind's lab on the role of a member of the Notch signaling pathway, "neuralized," in blood cell development, using the fly as a model. This City College Biology Department award of up to $2,000 is given to an outstanding student with an interest in cellular or molecular biology or microbial genetics.
Later, she worked in Johanna Joyce's lab at the Sloan-Kettering Institute. Funded by MARC and a sister federal program, RISE, Kester studied the interaction of macrophages, which are sentinels of the immune system, with cancer cells in mitigating the effectiveness of clinically relevant chemotherapies. The Joyce lab determined that macrophage-derived proteases (proteins that break down other proteins) can contribute to treatment failure in a mouse model of breast cancer.
She received other grants at City College: the Piel Award, the Josh and Judy Weston Scholarship, the Paul Krupa Award for Excellence in Research for her senior thesis defense. And she was a Howard Hughes Medical Institute-Pathways Investigator in Govind's lab.
As a rising senior in 2006, Kester won an NIH Fogarty International Center-MIRT (Minority International Research Training) grant, which sent her to Israel to work with Bedouin women to promote basic health care and their rights as Israeli citizens. "They have the right to health care and should get mammograms and Pap smears and testing for STDs," she says. "I organized a team with a social worker, a family-practice MD and a pediatrician to bring this group of marginalized Israeli citizens the health care they were morally and legally entitled."
Her work in Israel led to a heart-to-heart conversation with Govind, her City College mentor, about her original intention to pursue an MD/PhD program. "I was moved by the experience, but as amazing as it was, I realized my heart wasn't in medicine: I wanted to be at the bench. I love bench work, because it allows me to have a broader impact."
The 33-year-old Kester says she took some years off after high school before starting college at Hunter and then transferring to City. "I took my time graduating because I had two kids [now 4½ and 1½] in the middle," she says. "I did some modeling, worked at McKinsey [& Co., a global management consulting firm] as an IT analyst and then went back to school. So I went from modeling to model organisms."
What will she do after she finishes the National Science Foundation fellowship and earns her doctorate? She laughs. "The fellowship is a three-year grant, but I've started on what will be a 20-year project. I certainly hope to find the questions that we need to ask in three years, but answering them will take a lot more time."