DAVID TANK receives Brain Prize for advance in microscopy

PHOTO BY WINFRIED DENK

PHOTO BY WINFRIED DENK

David Tank, the Henry L. Hillman Professor in Molecular Biology and co-director of the Princeton Neuroscience Institute, has been named one of four winners of the Brain Prize, an honor that recognizes scientists who have made outstanding contributions to brain research.

Tank was presented the prize by His Royal Highness Crown Prince Frederik of Denmark on May 7, 2015, in Copenhagen. He shares the 1 million euro, or roughly $1,085,000, prize with Winfried Denk of the Max Planck Institute of Neurobiology in Munich; Arthur Konnerth of the Technical University of Munich; and Karel Svoboda of the Howard Hughes Medical Institute in Chevy Chase, Maryland.

The researchers were selected for the invention, development and application of two-photon microscopy, a technology that combines advanced techniques from physics and biology to allow scientists to examine the finest structures of the brain in real time.

“Thanks to these four scientists we’re now able to study the normal brain’s development and attempt to understand what goes wrong when we’re affected by destructive diseases such as Alzheimer’s and other types of dementia,” said Professor Povl Krogsgaard- Larsen, chair of the Grete Lundbeck European Brain Research Foundation, which awards the prize.

–By Michael Hotchkiss

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Engineering health solutions for all

Benjamin Tien

Benjamin Tien. PHOTO BY PETER LAMBERT

Hundreds of women die every day due to excessive bleeding after childbirth, but this can be prevented by an injection of the hormone oxytocin, which stimulates uterine contractions that reduce bleeding. Yet oxytocin must be kept cold, and developing countries often lack the resources to transport and store the hormone. Nor do they have enough trained personnel to administer the shot.

Benjamin Tien, who graduated from Princeton in 2015 with a degree in chemical and biological engineering, has been awarded a Fulbright grant to join a research team developing an aerosolized, inhalable version of oxytocin. He’ll work at the Monash Institute of Pharmaceutical Sciences in Australia to use a technique called “spray-drying” to turn liquid oxytocin into a dry powder that can be released from an inexpensive, disposable device. This would cut out the need for special storage conditions, eliminate the risk of infection from needles, and make the treatment available even to women giving birth at home.

While at Princeton, Tien conducted senior thesis research on nanoparticles for dealing with bacterial infections such as cholera or pseudomonas with Robert Prud’homme, a professor of chemical and biological engineering and Tien’s thesis adviser. During the summer before his senior year, Tien worked at a startup company in Boston called Diagnostics for All that develops medical diagnostics for developing countries.

While doing research in Australia, Tien will also work with the Poche Center for Indigenous Health, an organization that aims to improve the health of indigenous Australians with an emphasis on forming lasting relationships with the communities. “I want to get a better sense of the challenges people are facing on the ground, which will help me know what to focus on in my career,” Tien said.

-By Takim Williams

Tiny delivery capsules for new drugs

‘Jack’ Hoang Lu researches nanoparticles for drug delivery

Graduate student ‘Jack’ Hoang Lu works on engineering nanoparticles for targeted drug delivery and diagnostics in the laboratory of Robert Prud’homme, professor of chemical and biological engineering. PHOTO BY CATHERINE ZANDONELLA

Some drugs cannot be delivered via a normal pill or injection because they cannot readily dissolve in water. About 40 percent of new pharmaceuticals have this hydrophobic (water-fearing) character, and like a globule of oil in water, they are unable to reach their targets in the body.

Robert Prud’homme, professor of chemical and biological engineering, addresses this problem by putting the drugs inside of nanoparticles, each about one-thousandth of the width of a human hair, which are then covered with a polymer called polyethylene glycol. The small size enables dissolution of the drug to increase their bioavailability.

Nanoparticles can also tackle a different delivery challenge presented by a growing class of drugs called biologics that, as the name implies, are made from cellular or genetic components. The problem is that they are all water-soluble, which make them easy prey for patrolling proteins that identify them as foreign and degrade them. The solution is similar: nanoparticles protect the biologics long enough for them to carry out their mission.

In addition to increasing the time that drugs spend flowing through the body, Prud’homme’s nanoparticles are capable of targeted delivery. This is necessary in the case of toxic drugs, including many cancer treatments, which would damage healthy cells if allowed to roam freely throughout the body. Prud’homme puts appendages, called ligands, on the outside of his nanoparticles that, due to their specific shape and chemical properties, attach to their target and only to their target. In collaboration with Patrick Sinko at Rutgers University, Prud’homme’s group discovered the optimum density of an appendage called a mannose ligand, used to target cells harboring tuberculosis microbes. The unexpected result was that attaching more appendages to a nanoparticle decreased its targeting effectiveness. This demonstration of the complex interplay between engineered nanoparticles and how the human body responds to them is a major theme of the Prud’homme research team. In addition to tuberculosis, the researchers are using these principles to attack cancer, inflammation, and bacterial infections.

The project receives funding from the National Institutes of Health, the National Science Foundation, Princeton’s IP Accelerator Fund and the School of Engineering and Applied Sciences Old Guard Grant.

–By Takim Williams