Indian-American graduate student in Princeton hits the lights on cells’ development

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An Indian-American graduate researcher at Princeton University is leading a major study on cells, and her team has created a tool, combining light and a specific protein, that gives an unprecedented look at developing life forms.

According to a Dec. 5, 2019 press release from Princeton University, the study was led by Aleena Patel, a graduate student in chemical and biological engineering.

Combining light and a protein linked to cancer, this team of researchers have created a biological switch to conduct an unprecedented exploration of cellular development in the embryo, the University said.

The study, published Dec. 2 in the Proceedings of the National Academy of Sciences, “promises to help experts map precise cause and effect relationships in one of life’s most basic systems — the development of an amorphous embryo into a fully articulated life form,” the press release said.

The research tries to answer a critical question on how an undefined cell knows to become part of a toenail and not a brain stem? Scientists don’t understand this process very well, but they know it’s central in understanding disease and development.

Patel, the study’s first author, said that when signals misfire and the cellular control mechanisms veer off course, a wide variety of problems can emerge, including many developmental disorders and, later, the precursors of cancer.

“We want to know how these mutations are breaking not only the interaction networks within cells but also the developmental processes that are so tightly regulated in the entire embryo,” Patel is quoted saying in the press release.

The technique developed by them can be adopted widely, according to the team. Their current work focuses on signal timing. Their future work could look at spatial patterns,  the University said.

In their experiments, the researchers blasted proteins in developing zebrafish with a targeted pulse of light (a technique known as optogenetics), switching the proteins into their activated state. Each activated protein then sent chemical signals along a prescribed pathway into the cell’s center.

In normal development, these signals activate at just the right time and in just the right place, always in exactly the same way. But Patel and her team of researchers turned the switch on out of sequence, for long intervals, flooding the cell with its own signal and tracing the outcomes.

“I’m just taking advantage of what’s already there in nature, using nature’s design,” Patel said.

The Princeton team focused on a chain of chemical signals called the ERK pathway, one of only a few signaling pathways preserved over 3.5 billion years of natural selection. A vast number of developmental disorders arise from early problems in the human ERK pathway, including underlying causes of congenital heart disease, autoimmune syndromes, skeletal malformations and epilepsy. When ERK pathway problems occur in adult cells, they can result in malignant tumors.

Additional researchers included graduate student Eyan Yeung, undergraduate student Andrew Wu; Assistant Professor of Molecular Biology Jared Toettcher; and former undergraduate student Sarah McGuire, whose work on this project was the basis for her senior thesis.

This work was supported by the National Science Foundation’s Graduate Research Fellowship Program and the National Institutes for Health.