GRANT. Thaher Pelaseyed, who recently returned to Gothenburg after a postdoc at Cornell University, is now establishing his own independent lab, focusing on a new type of surface receptors in intestinal cells. He as just secured funding for the next four years, thanks to a generous grant from Swedish Society for Medical Research (Svenska Sällskapet för Medicinsk Forskning, or SSMF).
SSMF’s Large Grant goes to promising young scientists who are establishing themselves as independent researchers. The grant awarded to Thaher Pelaseyed totals SEK 6.8 million over 4 years.
“My group is focusing on a group of proteins located on intestinal surfaces. These proteins are glycoproteins known as transmembrane mucins, and their function is not well understood,” says Thaher, who has several exciting ideas about how the research can be pursued.
New receptors that “taste” bacteria
The transmembrane mucins extend like “bottle brushes” from small protrusions on the intestinal cell surfaces called microvilli. Transmembrane mucins are relatively long: a micrometer, or one millionth of a meter. During his time as a doctoral student in Gunnar C. Hansson’s lab, Thaher demonstrated that these transmembrane mucins can sense mechanical forces and that intestinal cells react by tucking awat transmembrane mucins when the intestine secretes mucus and water, for example during intestinal infection. Why the intestinal cells react in this way remains to be investigated. Recent studies have shown that transmembrane mucins are phosphorylated in the cell, indicating that they are involved in cell signaling.
“Our hypothesis is that the transmembrane mucins are a new type of surface receptors that intestinal cells use to ‘taste’ the gut microbiota,” Thaher says. “When bacteria penetrate the protective mucus layer of the intestine, these long transmembrane mucins are the first thing the bacteria encounter,” Thaher continues.
“I have demonstrated that there are bacteria and parasites that bind to transmembrane mucins, and even cleave them from the cell surface. We believe that bacteria in this way trigger specific signaling pathways in the intestine. The question now is which bacteria can bind and cleave transmembrane mucins, what kind of signaling is triggered and of course, what are the biological consequences for us humans.”
Because the transmembrane mucins have not been fully sequenced in mice, it is not yet possible to study the function of transmembrane mucins in animal models. In his experiments Thaher uses a cell line that behaves like intestinal epithelial cells. As a substitute for animal models, the lab will also use primary cells from mice that are first reprogrammed and then used to recreate the intestine in a laboratory setting.
Drawing inspiration from Ithaca
After receiving his PhD in 2012, Thaher moved with his family to the United States, where he spent two and a half years as a postdoc in Anthony P. Bretscher’s laboratory at Cornell University in Ithaca, NY. Members of the team, who came from all over the world, are experts in epithelial cell biology. Back in 1980s, Tony Bretscher discovered one of the proteins that controls how microvilli on epithelial cells are formed, and since then, his lab has identified the step-by-step mechanisms behind microvilli formation.
“Being a postdoc at Cornell was inspiring. Ithaca is a nice little university town, where the university is in an extremely beautiful location on a small hill overlooking a big lake. It’s a very vibrant research environment, with many seminars and spontaneous meetings. Research is a constant topic of conversation there.”
Both he and his family enjoyed Ithaca, and he misses the time at Cornell, he comments.
“As an international postdoc, I was is an unique and somewhat luxurious situation. As a graduate student, you’re under extreme pressure to deliver on your thesis, and now as I setting up a lab of my own, I won’t have as much time as I would prefer in the lab. I really enjoy doing experiments, and I easily become restless in front of the computer.”
Supported by the Wenner-Gren Foundations
Thaher has been back in Gothenburg for just over a year. The Wenner-Gren Foundations, who funded his postdoc in the U.S., have continued to support his research. With the aid of several other smaller grants, he is building a research team at Medicinareberget and has now secured his own funding for the next four years. His team currently consist of a postdoc and a student, and during the coming year an additional postdoc and a doctoral student will join the group.
TEXT AND PHOTO: ELIN LINDSTRÖM CLAESSEN