Alfredo Celedon, HHMI NanoBioMed graduate student. Credit: INBT / JHU
Nanoparticless open up enormous possibilities for scientists and engineers to study biomolecules, says Alfredo Celedon, a NanoBioMed graduate (pre-doctoral) trainee at the Johns Hopkins University Institute for NanoBioTechnology (INBT).
“The ability to tailor magnetic nanoparticles, connect them to a biomolecule, and use the magnetic nanoparticle to manipulate the molecule is a very powerful concept. It will allow us to study the way different enzymes work, and it may even allow us to use them in new ways,“ Celedon says. “Proteins are perfect nanomachines, so it would be great to find ways to take advantage of their mechanisms.“
The molecule of most interest to Celedon is chromatin, the complex of histone proteins and DNA that make up chromosomes in the nuclei of eukaryotic cells. Celedon is studying the mechanical properties of chromatin by observing chromatin condensation under different biologically relevant conditions.
“If you modify the histones, you change the way the chromatin behaves,“ Celedon says. “When the chromatin condenses, the structure is tightly held, and there is no access to the DNA. If the chromatin is less condensed, the histones are more loosely held, and access to the DNA is permitted. Cells control gene expression in this way.”
Using nanoparticles and magnetic tweezers, Celedon has been able to exert forces on the chromatin fiber to study its response. He hopes these experiments will shed light on the generally held hypothesis that there is a “histone code“ that guides interactions between enzymes and DNA.
Modified histones are prepared in the lab of INBT affiliate Greg Bowman, assistant professor of biophysics at the Krieger School of Arts and Sciences. Magnetic nanoparticles are fabricated in the lab of Peter Searson, professor of materials science and engineering and director of INBT. Experiments using the magnetic tweezers experiments are conducted under an inverted optical microscope in the INBT’s laboratory located in the Whiting School of Engineering. Celedon’s advisors include INBT affiliate Sean Sun, assistant professor of mechanical engineering, and Denis Wirtz, professor of chemical and biomolecular engineering and INBT’s associate director.
“I had previously attempted to model these concepts theoretically,“ Celedon says. “Through the guidance of my advisors and INBT, we have developed a way to test these ideas experimentally. This is my first experience using nanotechnology, and we found that it is a unique way to observe the behavior of chromatin.“
Celedon, a native of Chile, earned both a bachelor’s and master’s degree in chemical engineering from Catholic University of Chile. He first came to the U.S. on a Fulbright Fellowship to University of California, Los Angeles, where he earned a second master’s degree in bioengineering.
The NanoBioMed program is sponsored by the Howard Hughes Medical Institute. To learn more about the NanoBioMed HHMI program, click here.