The Next Phase

Since the late 19th-century the MDI Biological Laboratory has been a summertime incubator of scientific excellence. Starting in the early 2000s, a series of federal grants encouraged a new cohort of innovators to bring their research here year-round.

Now the Laboratory is pursuing a final allotment from one of those grants, to put its technological capabilities on a new level as well. The investment of more than $3 million in technical staff and infrastructure would add to MDIBL’s growing stature as a world-class resource for the study of aging, regeneration, and the repair of living tissues.

“One hundred years ago, scientists were asking the same questions, but they did not have the tools or the means to address

them,” says Prayag Murawala, Ph.D. “Now as the days are passing, new technologies are evolving. And these technologies enable us to answer these questions.”

Murawala is one of the early-career scientists whose research group was established with funding by the “Centers of Biomedical Research Excellence (COBRE)” grant program, administered by the National Institute of General Medical Sciences.

He’s a specialist in comparative biology and the axolotl salamander, which has astounding abilities to regenerate limbs, tissue and even its brain.

“The central question I and many colleagues across the world are focusing on is: how can these animals regenerate?” Murawala says. “And why can’t we do that?”

The Laboratory is seeking additional COBRE support for its animal husbandry core as it develops a wider array of transgenic model animals such as axolotl, zebrafish and African turquoise killifish. For MDIBL’s investigators, the animals are windows on cellular and molecular processes that point to new treatments for human injury, disease, and agerelated decline.

“We have been one of the leaders in developing these transgenic animals and we want to keep on that track,” Murawala says.

To open the research window even wider, the grant would enhance the Laboratory’s bioinformatics capacity and facilitate plans to build a half-million-dollar, stateof-the-art light sheet microscope.

The cutting-edge system provides unprecedented clarity and speed in the three-dimensional depiction of subjects ranging in size from the cellular to the molecular. It allows entire organs and organisms to be imaged, with the ability to close in on their anatomy at the cellular level — and from any angle.

Murawala says.

Recently pioneered in the Helmchen lab at the University of Zurich, it’s called “mesoSPIM,” for meso-scale selective plane illumination microscopy. MDIBL’s version will be one of only four like it in the U.S., and it will be available to a wide array of researchers in and outside of Maine.

With advice from one of the Zurich experts, Murawala is assembling the laserbased microscope alongside Marko Pende, Ph.D., a post-doctoral bioengineer in his lab. Pende studies how limb regeneration is regulated in axolotls, but he’s also an expert science imager who’s inventing new ways to “clear” tissue samples, making them transparent for easier viewing.

“What is the 3D architecture of the nervous system? What is the 3D architecture of a blood vessel?” Murawala asks. “These are questions that can only be answered if you do in toto imaging of your sample. Combined with our strength in tissue-clearing, mesoSPIM will be a game changer.”

And it’s a technological advance that the Laboratory will share with scientists and students around the state of Maine and beyond.

Frédéric Bonnet, Ph.D., who manages the MDIBL Light Microscopy Facility, says the system will be available to the entire network of 14 Maine education and research institutions that access the Laboratory’s infrastructure thanks to a linked federal program called the IDeA Network of Biological Research Excellence, or INBRE, for research and education.

180 facilities in the BioImaging North America network (BINA) will also gain access.

“Our overall goal is that the microscope will be open to everyone who wants to try it and to run a project,” Bonnet says. “We will establish a nationwide imaging service focused on tissue clearing and mesoSPIM imaging.”

And, he notes, the MDIBL’s dorms and cottages for visiting students and scientists can host researchers seeking significant time with the microscope. That would be another important element of the latest phase of the federal grant: funding for pilot projects proposed by outside researchers.

“We want people to come here and contribute, innovate and thrive,” says Iain Drummond, Ph.D., Principal Investigator for the MDIBL’s COBRE awards. “We want young people to go on and seed the rest of the country with groundbreaking discoveries, systems of discovery. It’s ongoing — generating the next generations’ innovators.”