Princeton University professors winning Nobel prizes for their research is a fairly regular occurrence, and researchers publish papers in peer reviewed journals all year round, advancing knowledge on all fronts. But in the last few years, the university has been encouraging a different kind of work: the kind that can be patented and make its way out of the lab and into the marketplace on a time scale faster than decades.
Rodney Priestley, a professor of chemical and biological engineering and, beginning in February, 2020, Princeton’s first vice dean for innovation, says the efforts to encourage technology commercialization have been having the intended effect. Over the last few years, faculty-led spinout companies have gone from one or two a year to eight to 10, he said. Recent developments such as the creation of the Princeton Biolabs on College Road East are intended to further accelerate this trend.
The university is hosting an event to show off some of these innovations on Thursday, November 14, at 5 p.m. at the Frick Chemistry Lab Atrium. For more information, visit innovation.princeton.edu/event.
For the first eight years of its existence, this annual showcase was called “Celebrate Princeton Invention.” But two years ago the invention turned to “innovation” to match the business world’s use of the latter term to refer to marketable inventions. “It reflects a growing emphasis on the university not only being good at fundamental research and invention, but also to be good at translating those inventions to practical use,” Priestley said. “The projects the university is seeking to highlight are those that are rooted in fundamental science but which are not 30 years away from having an impact: they are going to have an immediate impact that can be seen.”
Some of these inventions are being turned into companies.
One such invention came out of the lab of life sciences professor Thomas Shenk and molecular biology professor Ileana Cristea, who discovered a new way of fighting viruses using a protein called a sirtuin. In 2013 Shenk’s wife, Lillian Chiang, turned that discovery into a company called Evrys Bio, which is dedicated to turning that lab discovery into therapies that can be used to cure all kinds of viral diseases.
The nine-person company is located in a tech incubator in Doylestown, Pennsylvania. Chiang says product development has reached the point where it is being tested on animals, the last step before trying it out on human subjects.
Her hope is that within five to eight years, sirtuin-based treatments for viruses could be approved for human use. If it proves successful, the technology could save thousands of lives per year.
The product farthest along is for organ transplant patients. Because anti-rejection drugs suppress the immune system, there is a serious risk of viral infection, and about 40 percent of transplant patients end up suffering from it. Chiang’s team used human chimeric mice (mice with human cells transplanted into them) to test out their drug-like molecule against the very common cytomegalovirus, and found it was effective.
At the same time, Evrys is collaborating with researchers at other institutions to test it against influenza and the Marburg virus, a disease similar to Ebola that is usually fatal. Chiang speculates that it might also be effective against rabies, which is nearly always fatal if the victim doesn’t get a vaccine in time.
Chiang, who grew up in New Jersey with an engineer mother and professor father, earned her doctorate at MIT and an MBA at Wharton. She previously worked at two other biotech startups. Evrys is her first collaboration with her husband, whose lab has been responsible for numerous spinoffs since the 1980s.
“It’s always a long haul to get an idea off the bench and into the clinic,” Chiang says. “You run into all kinds of barriers: scientific risk, clinical risk, product risk, and ultimately, financing. For me the company represents a chance to take something from the bench to the clinic.”
The first major obstacle Evrys had to overcome was skepticism about its technology. Unlike most other antiviral drugs in development, Evrys’ product targeted the host cells rather than the virus itself. But the success of immunotherapy against cancer served as a proof of concept that using drugs to turn the body itself against a disease could be an effective strategy.
Chiang says the company will enter clinical development next year, and after that human trials can begin. But success is not guaranteed. “Things always take twice as long and twice as many dollars as you initially think,” she says.
Another innovation on display is intended to save energy rather than lives. Civil and environmental engineering professor Sigrid Adriaenssens and post-doctoral research associate Victor Charpentier were inspired by the way certain plants move to follow the sun throughout the day and created a system of “smart shades” that can be attached to windows and automatically provide the optimal amount of light and shade while blocking glare and allowing maximum visibility for the room’s occupants.
“Nature is very resourceful in using very little material and very little energy,” Adriaenssens said. “We use very little energy to power the device.”
She said she and Charpentier were inspired by one particular plant that had an interesting mechanism to move around. The resulting invention uses two wires, one which twists the sheet, and the other that bends, which can be combined to move in any direction.
The shades consist of flexible plastic sheets that are bent by shape-memory alloy wires. An advanced algorithm allows the sheets to always bend to follow the sun at any location on the planet, for a window facing any direction on any day of the year and at any time of day.
Adriaenssens says they have even created a way to manufacture the system cheaply.
There are still decisions to be made: for example, would the shades be on the outside of the building? Or would they be on the inside, like conventional blinds, and able to be rolled up when they aren’t wanted? They are also considering placing them between two panes of glass on double-sided windows.
The potential energy savings from using the smart shades are enormous. Most of the time people leave their shades in one position or very seldom change it. This means that rooms are sometimes shaded in the winter, making the heating system work harder to keep up, or let too much sun in during the summer, causing the air conditioning to kick in to keep a comfortable temperature.
Adriaenssens notes that 40 percent of all the world’s energy use is from buildings, and she says that smart shades could make a building use 50 percent less energy for heating and cooling. She is working with the university’s office of technology transfer to find a company to license the invention.
“This device coupled together with the algorithm could be part of the smart home revolution,” she said.
“All of the innovations that are coming from inventors at Princeton are rooted in pure and applied fundamental research,” Priestley says. He says the push to get more of that research out into the real world has not affected the university’s research priorities. “I think it has added energy to existing priorities now that we can foresee direct impact from some of the work they are doing,” he says. “We have always wanted our research to have an impact. We’re doing more to make sure that it has an impact.”
A sampling of the many other innovations on display at the event include:
A. James Link: Lasso-shaped antibiotic for the treatment of lung infections. A new antibiotic compound with an unusual shape is on track to treat deadly drug-resistant lung infections that are commonly associated with cystic fibrosis. The antibiotic is a type of “lasso peptide,” a short protein segment named for its resemblance to a loop of rope. The newly developed antibiotic, dubbed ubonodin, selectively kills bacteria of the genus Burkholderia, which includes many members that are resistant to conventional antibiotics.
Developed by chemical and biological engineering professor A. James Link and graduate student Wai Ling Cheung-Lee, ubodonin’s distinctive shape makes it highly stable in both dissolved and dry forms across a range of temperatures. The molecule targets Burkholderia by stopping cell replication through the inhibition of the enzyme RNA polymerase. The molecule is highly specific against Burkholderia strains, which is advantageous because the molecule does not kill off beneficial bacteria.
The team has demonstrated the ability to produce ubonodin by introducing a novel DNA sequence into E. coli. Having shown that the molecule can kill Burkholderia cepacia, which causes lung infection, the team is now working on ways to engineer the molecule to target other pathogenic Burkholderia strains.
Jeffrey Schwartz and Jean Schwarzbauer: Nerve damage repair using a patterned extracellular matrix. A new recipe for patterning cells on a surface holds promise for the repair of damaged nerve tissue. Researchers Jeffrey Schwartz, a chemistry professor, and Jean Schwarzbauer, a molecular biology professor, have developed a technique for adhering and aligning cells on a soft and flexible material, known as hydrogel, with the goal of creating a scaffold on which to grow neurons and provide guidance for the cells to extend the long thin projections, or axons, that serve as the transmission lines of the nervous system.
A key challenge was to find ways to make cells stick to hydrogel, a material that consists of a watery synthetic or natural polymer that resembles not-yet-set gelatin. To overcome this challenge, the researchers engineered a method for applying a cell-adhesive layer atop the hydrogel. By initially masking parts of the hydrogel surface, the researchers can create precisely defined sticky regions, enabling cells to be patterned, and to assemble a patterned extracellular matrix in arrangements that are useful to neural repair.
Yiguang Ju: HiT Nano Inc. makes high-performance batteries affordable. A new method for making high-nickel and cobalt-free lithium-ion battery materials promises to increase performance for markets such as electric vehicles and grid energy storage while increasing battery density and battery life, all at lower cost. To develop the technology, mechanical and aerospace engineering professor Yiguang Ju and his team founded the startup HiT Nano Inc. in 2018.
HiT Nano uses a novel, patented mechanism invented in Ju’s lab at Princeton called micro-aerosol controlled high temperature (MACHT) synthesis to generate nickel-cobalt-magnesium and other high-nickel nanoparticles for battery cathodes, the positively charged side of the battery that supplies current.
Today’s commercial cathode manufacturing methods produce particles using a long, multi-step co-precipitation process. In contrast, MACHT is a single-step flame synthesis process. The resulting higher yield, lower cost, and improved performance have the potential to lead to dramatic boosts in battery storage capacity and reductions in recharging times.
Minjie Chen: Technology to boost energy efficiency in data centers. Electrical engineering professor Minjie Chen and his team are building a family of devices to dramatically reduce power consumption at the gigantic data centers that serve as the backbone of internet services and cloud computing. These centers, each holding racks of computer servers, consume 90 billion kilowatt-hours of electricity each year in the U.S.
The team’s technology restructures the way power is converted from the 480-volt alternating current of the electricity grid down to the 5-volt-or-lower direct current needed for central processing units and hard drives. In today’s data centers, this process happens at each computer, sapping about 40 percent of the original energy. Chen and his team are building a new energy processor that reduces the voltage in a central unit, then simultaneously supplies power to a large number of computing devices.
Instead of lots of cascaded power conversion stages, they aggregate power conversion into one unit, and then distribute that power. They estimate they can increase the energy efficiency of the power-delivery system from about 60 percent to 88 percent. The technology also works with solar farms and battery storage systems.
Esteban Engel: Novel gene-delivery technology for treatment of disease. A newly developed system for turning on the therapeutic activity of genes could benefit the treatment of a broad range of genetic diseases. Princeton Neuroscience Institute researcher Esteban Engel and his team have developed gene promoters, which act like switches to turn on gene expression, to enable the creation of a wide range of gene therapies with long-lasting therapeutic effects.
The team has engineered three new promoters that are inserted into the adeno-associated virus (AAV), which is widely used to deliver therapeutic genes into cells. These promoters occupy far less space than the promoters in use today, allowing the viral vector to carry larger genes. These novel promoters are also less prone to repression or inactivation than most common promoters, so they sustain gene expression for long periods of time.
Mala Murthy and Joshua Shaevitz: AI-based motion-capture system for lab animals. A new system that uses artificial intelligence to track animal movements is poised to aid a wide range of studies, from exploring new drugs that affect behavior to ecological research. The approach can be used with laboratory animals such as fruit flies and mice as well as larger animals.
The technology, developed by Mala Murthy of the Princeton Neuroscience Institute, physics professor Joshua Shaevitz, graduate student Talmo Pereira, and Diego Aldarondo of the Class of 2018, accurately detects the location of each body part — legs, head, nose and other points — in millions of frames of video.
A human experimenter records video of a moving animal then directs the system’s software to identify a small number of images in which to define body part positions. The system then uses this dataset to train a neural network to calculate the location of the points in subsequent frames.
Amit Singer: Software for near-atomic resolution using cryo-electron microscopy. A software package aims to aid drug design and biomedical research by making it easy to construct 3D images of proteins and other molecules using one of the world’s most powerful microscopes. Amit Singer and his team are developing a package they call Algorithms for Single Particle Reconstruction, or ASPIRE, that takes in 2D images captured by cryo-electron microscopy and produces reliable 3D structures without significant human intervention.
The package will offer fully automated and faster data processing, producing highly accurate images. Whereas existing software packages require human input on which images to include in analysis, ASPIRE needs little user modification, reducing the potential for bias. The team’s long-term goal is to develop a commercial software package that will make biomolecular structures more readily available for drug discovery and research.