Illustration by Nevya Hernandez
The trillions of cells that constitute our bodies usually contain the same genetic information encoded within DNA molecules, the universal marker of identity known to determine its carrier’s traits and function. And yet, there exist hundreds of different cell types with diverse shapes and functions. What then, if not genetic information, differentiates these different cell types from each other?
The Percipalle Lab at NYU Abu Dhabi, headed by Professor Piergiorgio Percipalle, seeks to understand the cryptic process called cellular differentiation, which occurs when a cell undergoes a transformation into a specific kind of cell. Cells that have the potential to undergo differentiation, like zygotes and stem cells, are said to be undifferentiated, in contrast to differentiated cells like neurons, which have already gone through this process.
Currently, we understand differentiation as the process in which an undifferentiated cell like the zygote or stem cell activates certain genes and represses others depending on the cell type it will differentiate into. What remains unclear, however, is the exact mechanism of this process — what occurs within the cell that causes it to transform into a specific cell type — which is unique to each individual cell type. Uncovering the complex molecular mechanisms that occur during cellular differentiation is exactly what Percipalle and his team of four postdoctorates seek to understand.
“We are interested in gene regulation and genome organization during development and differentiation,” said Percipalle. “We are interested precisely in these mechanisms during neurogenesis during which cells become neurons.”
Percipalle has been invested in research on gene expression since 2004, the year he set up his first independent lab thanks to a grant from the Swedish Research Council. He became an independent investigator at the Karolinska Institute Department of Cellular and Molecular Biology in Stockholm, Sweden, which is when he developed his own line of research. After spending 16 years at the Karolinska Institute, Percipalle calls Stockholm the place he “grew up as a scientist.” It was around early 2015 when Percipalle heard of an opportunity at NYUAD.
“I was very curious at the time because I wanted to look into other options. The Karolinska Institute is a medical school and so you have a lot of people who go there with medical or biomedical research, but I wanted to look into a broader perspective,” he said.
By fall 2015, Percipalle started setting up his lab at NYUAD while still remaining in contact with the Karolinska Institute.
The facilities available at NYUAD provide Percipalle with necessary tools to carry out his research. To investigate cellular differentiation during neurogenesis, Percipalle uses fibroblasts, skin cells that constitute connective tissue, which are only partially differentiated.
“We set up a protocol to induce neurons from fibroblasts, and then we can see how genes are switched on and off during the process. We are also setting up protocols to do this in a stepwise manner so that we can de-differentiate [neurons] into neuronal stem cells [and] then re-differentiate them back into neurons. That’s the beauty of working with fibroblasts,” Percipalle explained.
Using a combination of genomic techniques made possible by the variety of equipment available at NYUAD such as transcriptomics and bioinformatics, Percipalle is able to determine which genes are activated and how often gene activation occurs.
In addition to the aforementioned genomic techniques, Percipalle said that he applies “advanced imaging techniques that really allows us get insights into the cell, thanks to the great facilities in terms of advanced microscopies.”
Understanding differentiation is important because it explains how different types of cells are able to arise. Furthermore, though Percipalle stresses that this can only happen in the long term, his research also has several medical applications.
“By doing this type of analysis we are understanding differentiation better and better,” he said. “What we are interested in is the biological process, the question of differentiation. If we can master and understand how this happens, then of course we can experiment more.”
Nathan Quimpo is Deputy Features Editor. Email him at [email protected]