After her return to Santiago de Chile, Fabiola Osorio, an alumna of the VIB-UGent Center for Inflammation Research, was selected to be among the first group of HHMI International Research Scholars. Together with 40 other scientists from 16 countries, she was chosen from a pool of 1,400 candidates as an ‘exceptional early-career scientist poised to advance biomedical research across the globe’. With the recognition comes a five-year research grant worth $650,000.

Can you tell us more about the HHMI International Research Scholar program?
“Alongside the Howard Hughes Medical Institute, the Bill and Melinda Gates Foundation, the Wellcome Trust in the UK and the Calouste Gulbekian Foundation in Portugal were involved in this initiative. These four philanthropic institutions teamed up to create this special grant for young scientists with creative projects. However, the program funds people, rather than specific projects,” explains Fabiola Osorio.

Which researchers can apply?
“To be eligible, you have to be trained in the US or the UK, be an independent researcher for fewer than 6 years and conduct your current and future research in a non-G8 country.”

“For me, it was an opportunity that suddenly popped up. As an assistant professor and young PI, I was continuously looking for money to set up and expand my own lab. I was pre-selected and invited to the Wellcome Trust in London for a three-minute presentation in front of a jury of experts from many different disciplines. And fortunately, I hit the jackpot,” Fabiola laughs.

At the same time, she admits: “I have been so lucky, though! First of all, I was trained in Caetano Reis e Sousa’s lab at the Cancer Research UK –UCL Centre. Caetano is a leading immunology researcher. And
then, when working in London, Bart Lambrecht crossed my path. He had this provocative idea to study the role of cellular stress in immunity and gave me the opportunity to do a postdoc in Ghent from 2011-2013. It was in his lab and under his mentorship that I defined my current line of research, which also formed the basis for the HHMI application.”

Is this research line linked to the Nature Immunology paper that you published together with Bart Lambrecht and Sophie Janssens in 2014?
“Absolutely. We discovered that a very basic biological mechanism in homeostasis, the unfolded protein response (UPR), is one of the key regulators of dendritic cell activity in modulating the adaptive immune response to foreign invaders as well as tumor cells and in autoimmunity,” explains Fabiola. “The accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER stress. Three molecular sensors trigger this response. One of them is IRE-1alpha. We found that dendritic cells spontaneously turn on this arm of the UPR in the absence of ER stress and that this mechanism is crucial in the activation of dendritic cells.”

“This paper was the start of a completely new research line for me: understanding the interactions between cellular stress, preserving cell homeostasis, and regulation of the immune system. In the last 20 years, we’ve learned a lot about the processes triggering inflammation, but we barely know anything about how inflammation is regulated or stopped.”

What are the potential clinical consequences of these new insights?
“These pathways may play a decisive role in the anti-tumor immune response. The tumor environment – with its low oxygen availability and high demand for energy – is highly stressful for dendritic cells. Dendritic cells control essential processes in the anti-tumor response, including antigen presentation and induction of T lymphocytes. This is just one example, but it’s likely that intracellular stress is involved in calibrating the immune response in inflammation and infection contexts.”

“I am convinced that we are making history with this new field of immunology,” concludes Fabiola, “at a time when most discoveries will generate completely new insights. For this reason, I stay in close contact with Sophie and Bart. The VIB-UGent Center for Inflammation Research is not just an advanced research lab; it’s also a warm social environment. This unique combination makes VIB an ideal place to pursue scientific research. From the moment I arrived in Ghent, I felt at home. In retrospect, I can even appreciate Belgian weather!”