Kilachand Fund Awards Go to Crystal Rib Cage and Brain Connection Projects
Winners of 2023 interdisciplinary research fund grants aim to improve study of lung disease and brain development
When infection or disease strikes the lung—cancer, pneumonia, COVID-19—it’s tough for researchers to see what’s going on inside the organ. Even if they simulate in a lab the disease in a lung, they can’t recreate the forces the rib cage places on it without blocking their view of what’s happening. That’s about to change.
A crystal rib cage, developed by a Boston University engineer—and being refined in collaboration with a BU medical researcher specializing in pneumonia—will enable scientists to visualize in real time how the lung develops immunity against infection.
“This innovation will enable us to visualize the entire lung with an optical microscope at different scales, from cell level all the way to the entire organ,” says Hadi T. Nia, a BU College of Engineering assistant professor of biomedical engineering.
The crystal rib cage is one of two projects to win a 2023 Rajen Kilachand Fund for Integrated Life Sciences & Engineering award.
Since its launch in 2017, the fund has awarded $14 million to support projects that have advanced science, built collaborative structures for interdisciplinary research, and expanded funding opportunities. Past Kilachand award winners have made important scientific breakthroughs, secured patents, founded companies, and sparked important spin-off research.
“Our research is exactly the type of interdisciplinary work the Kilachand Fund was designed to support,” says Joseph Mizgerd, a BU Chobanian & Avedisian School of Medicine professor of medicine, who is leading the crystal rib cage project with Nia. “Hadi can engineer systems that allow us to study lungs in ways that nobody else on Earth can. And I have immunological and respiratory infection expertise from decades of work on this topic. Working together, we can potentially transform how pneumonia is treated, and possibly other respiratory diseases and cancer.” They were awarded $500,000 per year for up to three years.
BU trustee Rajen Kilachand (Questrom’74, Hon.’14) established the fund with a historic gift of $115 million with the aim of driving solutions to some of the biggest challenges in the life sciences, including heart disease, cancer, and degenerative brain diseases. The second 2023 winning project will investigate genetic and neuronal networks of healthy and diseased brains.
Defending against Pneumonia
A result of respiratory infection, pneumonia is a massive public health concern and more common among the elderly and in children. “Pneumonia is the number one cause of death globally for children under five,” says Mizgerd. “In the US, it’s the top cause of hospitalization for children under 9, as well as the top cause of death for hospitalized people over 65 years of age.” A person’s age and history of prior infection are two key factors contributing to the incidence and severity of pneumonia.
But scientists aren’t sure why some people have immunity when others don’t. Mizgerd says that understanding the impacts of age and prior respiratory infections on someone’s immune response to pneumonia has been a long-standing challenge. People can be exposed to the same microbe and have vastly different outcomes—a phenomenon also seen with COVID-19. “There’s something different within us that determines the outcome of these respiratory infections,” says Mizgerd, “and we’re trying to understand exactly what those differences might be.”
The crystal rib cage “will allow us to visualize every step of disease progression in real time,” says Nia. The researchers will also test how changes in the bloodstream and within the lung itself impact immunity. “In addition, we can evaluate the role of cells that are resident in the lungs and those circulating inside the bloodstream in order to evaluate how differences in age and infection experience affect immunity.” That deeper understanding of exactly how immunity against pneumonia works could help inform further studies on prevention and treatment, from improving vaccines to developing new therapeutics.
Understanding Connections in the Brain
The brain is a complex network made up of thousands of cell types, each expressing a different set of genes. While these patterns of gene expression are associated with cellular connectivity, information processing, and susceptibility to disease, scientists still don’t fully understand how they work. This year’s other Kilachand Fund award winners intend to change that with a new approach to exploring how genes express themselves in the brain.
The traditional way of defining the impact of genetic expression on brain development and disease involves taking out one gene at a time from an animal and then seeing what happens. Does its brain wire up correctly or does it end up with a disease? “The downside of this classic approach is that it’s just very, very slow,” says Michael Economo (ENG’12), an ENG assistant professor of biomedical engineering. “And disease states often have multigenic sources, so isolating just one gene is limiting.”
Instead, Economo and his colleagues are trying a novel investigative approach, building upon a technique called Perturb-Seq, which allows researchers to perturb (in other words, to prevent from working) multiple genes at once in a bunch of cells. The team’s goal is to pool technologies developed in their respective labs to create a new toolkit—a platform they call Spatial Interrogation of Neurons and Genes, or SING—for better understanding connections in the brain.
The investigators will work to interpret not just how the manipulation of genes changes gene expression, but also how these changes impact cell connection and disease progression. “This is a very enabling technology that builds upon new developments across a number of different domains, including in experimental neuroscience, molecular genetics, virology, and more,” says Economo, who is leading the project with Jerry Chen, a BU College of Arts & Sciences associate professor of biology, and Brian Cleary, a Faculty of Computing & Data Sciences assistant professor.
The trio views its work as potentially applicable “for investigating a large number of problems across domains, including the development of the normal functioning of the brain, how the brain wires its connectivity, and what happens in disorders of the nervous system,” says Economo. “We’re trying to attack those problems in a way that hasn’t been possible before.”
The research being done by Economo, Chen, and Cleary is high risk, but has the potential for big rewards—it’s very new, highly interdisciplinary, and could open up lots of fresh ground for other researchers. The team has been awarded $250,000 per year for up to two years.
“Federal funding agencies are so often hesitant to support this kind of research,” says Economo, “but funding from the Kilachand award has been vital for seeding so many new ideas across multidisciplinary interests and expertise. We couldn’t do this work without the fund’s help.”