Imagine being able to watch the smallest units of life-like cells and molecules-working together in real time. Seeing and measuring biological processes, a field called dynamic imaging, can help scientists unlock tremendous knowledge for treating diseases, from cancer to Alzheimer's.
In an effort to take biological imaging to the next level, two Boston University College of Engineering researchers are spearheading projects aimed at finding better ways to visualize the cellular mechanisms that drive our everyday life. Ji-Xin Cheng and Lei Tian will each receive more than $1 million in funding from the Chan Zuckerberg Initiative (CZI), a highly competitive program, to develop new methods for seeing cells, molecules, proteins, and neuron networks in real time.
"We are delighted to have received two grants in the area of dynamic imaging from the Chan Zuckerberg Initiative," says Gloria Waters, BU vice president and associate provost for research. "This is an area we have been investing in and this funding acknowledges the significant strength of our faculty in this area."
Cheng, an ENG professor of biomedical engineering and of electrical and computer engineering, is slated to receive $1,360,955 to lead a project that will harness the properties of infrared light and chemical bonds to track molecules inside cells. Tian, an ENG assistant professor of electrical and computer engineering and biomedical engineering, will be given $1,310,540 to develop a "computational mesoscope," an imaging platform to track in real time specific biological activity within cells and networks of cells, such as neurons in the brain. The two recipients, both experts in their fields, work closely together and recently published a paper that combined their expertise in computational and chemical imaging.
"This grant program is extremely selective and competitive," says Kenneth R. Lutchen, ENG dean and a professor of biomedical engineering. "Both efforts show the power of convergent research and synthesizing approaches from multiple disciplines to advance powerful new solutions for understanding disease."
To see molecules, Cheng and his team, which includes Tian and Bing Xu of Brandeis University, are developing a new dynamic imaging technique, called bond-selective intensity diffraction tomography (BS-IDT). This technique relies on identifying the chemical bonds of different molecules, then shining infrared light to excite the molecules and cause a property change at a specific location of a cell. By measuring the specific location of the change, they can produce a three-dimensional chemical map of the cell.
"Molecules are the foundation of life," says Cheng. "We want to know the location and dynamics of molecules in the three-dimensional cell, and understand how molecules communicate and play this elegant orchestra inside the living system."
With CZI's funding, Cheng and his team will work on refining the technique so they can get a clearer picture of the exact location of molecules. Eventually, they will be able to track the progression of different types of diseases, like Alzheimer's disease, and answer important questions, like how disease-causing protein aggregation begins in the brain. Cheng also hopes to use his technique to see inside cancer cells. "We can answer all kinds of questions if we can visualize these molecules," he says. This can lead to understanding how cancers become invasive or resistant to treatment, and provide new targets for treatments.
"Our method has the potential to discover hidden molecular signatures. And if we can do that, we can provide new targets for drug development," Cheng says. "This has enormous potential. I certainly appreciate CZI giving us this opportunity to pursue this kind of cutting-edge research, to do something that was not possible before."
Tian and his team, which includes Abdoulaye Ndao, an ENG assistant professor of electrical and computer engineering, and Sixian You of Massachusetts Institute of Technology, are aiming to develop an imaging platform that can similarly lead to new treatments and targets for drug development. Current systems to image biological structures-like fluorescence microscopy, which allow scientists to visualize how molecules are assembled inside a cell-are far from perfect, Tian explains.
There are trade-offs between the field of view, spatial resolution, imaging speed, and system complexity. His project would make biological imaging extremely fast, with a larger field of view and high resolution. Plus, it would be small enough to place on animals. The computational mesoscope will be miniaturized compared to current tools and lightweight enough to be used as a head-mounted device on animals, measuring neural dynamics while an animal is thinking and performing different behaviors.
This could have an "immediate impact on our ability to visualize network-scale neural activity, which is critical for a more integrative understanding of brain functions," Tian says. "My long-term vision entails combining novel hardware and advanced algorithms for 4D recordings of biological activities across large fields of view and depths."
The funding from CZI will bring Tian and his team closer to making his vision a reality.
