September 26, 2016

Scientists Discover New Means of Modeling Cell Development

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Between the cracks in the sidewalk sprouts a thin, green stem with fragile white flowers. It is overlooked by the masses of people who walk past it each day. Unknown to these individuals, however, is the significance of the Arabidopsis plant within the scientific community.

In her lab, Prof. Adrienne Roeder, a Nancy M. and Samuel C. Fleming Term Assistant Professor at the Weill Institute for Cell and Molecular Biology, uses the Arabidopsis sepal as a model system to study the spatial and temporal development of cells. Sepals are the part of the plant that encloses the flower. Despite the uniform growth of the four sepals enclosing a flower, their individual cells have variable sizes and growth rates.

This past summer, the Roeder Lab authored a paper, titled “Variable Cell Growth Yields Reproducible Organ Development through Spatiotemporal Averaging,” published in the peer-reviewed scientific journal, Developmental Cell.

Lilan Hong, a postdoctoral associate in the Roeder Lab and a first co-author on the recently published paper, conducted a mutant screen to search for the gene in the organism. The mutation disrupted the uniformity of the sepal growth observed in the wild flowers.

Both Roeder and Hong attribute much of their success to the interdisciplinary nature of their research, which is made evident by the different focuses of the three first authors of the paper, Hong, Mathilde Dumond, a graduate student in the Biophysics and Development department at Ecole Normale Supérieure de Lyon, France and Prof. Satoru Tsugawa, from the Research Institute for Electronic Science at Hokkaido University, Japan.

“Our research was made possible by collaboration between biologists, physicists and computer scientists [and] the interaction between data and models,” Roeder said.

The research conducted by the lab primarily makes use of three different technologies. Confocal microscopy is a form of microscopic imaging designed to improve focus by eliminating additional light. It is utilized for live imaging of growing sepals. Morphographics, a software designed by Dr. Richard Smith, is used to create models from data in order to analyze the images taken every 12 hours of the growth of sepal cells. Finally, the project relied on computational modeling to represent the dynamic variability in stiffness of the growing sepal.

The initial mutant screen, conducted by Hong, was used to create a mechanical model to look for the specific defect in the mutant. Morphographics was then utilized to develop models to more closely analyze growth rates. Further data analysis on the growth of the Arabidopsis sepals conducted by Prof. Chun-Biu Li, Research Institute for Electronic Science at Hokkaido University provided further insight into the variability of growth. The four sepals surrounding the flower grow uniformly, but their respective cells need not do so in order for the structures to form simultaneously.

“The cells were less variable in space, but equally in time,” Roder said.

The cells underwent spatiotemporal averaging, which is growth taking into consideration dimensions of space and time. However, despite differences in the sepal’s growth in the short term, there was greater similarity over a 48 hour period between the four sepals of each flower.

“A good model needs to be able to predict,” Hong said. “Results are then verified experimentally.”

From the results of their study, Roeder and Hong were able to see the close alignment of the model and wild type organism.

Though their paper has received significant acclaim in the scientific community, Roeder acknowledges that there are many ways to investigate the questions posed by cell growth, development and variability.

“This is universally broad question,” Roeder said. “Spatiotemporal averaging exists in many different systems.”

This variability also exists in the fruit fly during gastrulation — a stage of embryonic development.

The lab is aiming to further investigate the mutant from Dr. Hong’s screening, which is suspected to be a mitochondrial mutant. The mitochondria is responsible for energy production in a cell.

An experiment in which Vitamin C was used as an antioxidant treatment to rescue these mutants was also conducted, however, it was not included in the final draft of the published paper. Investigating these mutants further could lead to additional understanding about the development of these cells. In addition, investigating the equally broad question of stimulating organ growth is a long-term goal of the lab.

For the lab, the paper has been a remarkable feat.

“We are a new lab,” Dr. Hong said, “and being published in a high-profile publication while promoting [the] sepal as a model system has been important.”

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