Published: March 3, 2016
Bradley Wierbowski, a graduate of the class of 2013, recently returned to The University to present his current research. Wierbowski, a former Goldwater Scholar and current third-year Ph.D. student, studies in the Adrian Salic Lab in the department of cell biology at Harvard University Medical School.
While at The University, Wierbowski majored in biochemistry, cell and molecular biology (BCMB) and English.
“He excelled both in the sciences and in the humanities,” George Gomez, Ph. D., Wierbowski’s research advisor at The University said. “It was this ability that enabled Bradley to find new and unique ways of viewing a scientific problem.”
Wierbowski’s research centers on the role of a protein called SCUBE2, which functions in the vertebrate Hedgehog signaling pathway. Though he first learned about this pathway in his developmental biology class here at The University, Wierbowski explained that he did not fully appreciate how little scientists understand Hedgehog signaling on a molecular level.
“It’s easy to forget that what we learn in a textbook is just a snapshot of what we think we know at any given time in a field of interest,” Wierbowski said.
Since cells cannot directly speak to each other, cells rely on signaling pathways to communicate with each other. In signaling pathways, a sending cell sends a signal, which can include neurotransmitters, hormones or proteins, to another cell, which receives the signal and then acts upon it.
The Hedgehog signaling pathway uses a protein called sonic hedgehog (SHH) as the signal molecule in the cell signaling pathway. A sending cell secretes SHH and sends it to a receiving cell. The Hedgehog signaling pathway is integral in organismal development. For example, the Hedgehog signaling pathway is known to play a role in ensuring that each specific finger on your hand develops properly.
While still in the cell, SHH is modified by cholesterol. The cholesterol becomes attached to SHH. Cholesterol is a lipid, which is a hydrophobic, or water-fearing, molecule. Just like oil does not want to mix with vinegar, cholesterol and other lipids do not want to interact with the aqueous environment that surrounds the cell.
A cell’s outer membrane is also made of lipids, so the cholesterol inserts itself into the membrane to avoid the cell’s environment. Since SHH is attached to cholesterol, it also becomes stuck to the membrane. However, this poses a problem, since SHH is supposed to be able to leave the cell and act as a signal to other cells. That is where SCUBE2 comes into play.
Its function is to release SHH from the sending cell’s outer membrane and allow SHH to signal the receiving cell. A researcher in Wiebowski’s lab determined SCUBE2’s role by looking at cells with and without SCUBE2. The cells that expressed SCUBE2 also released SHH, but the cells that did not express SCUBE2 did not release any SHH.
Wierbowski’s research focuses on how SCUBE2 recognizes and binds the cholesterol molecule attached to SHH and how SCUBE2 binds to SHH. He is currently examining the different parts of SCUBE2, called domains, to see which are important for cholesterol binding. By removing different domains of SCUBE2 and examining the effects that has on SHH secretion, Wierbowski can determine which domains are essential to SCUBE2 function. Wierbowski also hopes to look at what happens to the SHH/SCUBE2 complex after it is released from the cell and how a receiving cell receives the SHH signal.
Wierbowski was happy to return to The University to share some of his work with students and faculty. In his presentation, Wierbowski stressed that different fields of science are often needed to answer a specific question. Wierbowski’s research draws from genetic approaches and uses cellular and biochemical techniques to answer his questions.
When asked about what he wanted people to know most about research, Wierbowski explained, “One of the challenges of research is learning how to ask the right kind of question for the approaches that you use and also recognizing when you need to branch out and learn new techniques to answer a question that interests you.”
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