December 19, 2014

Progress Report on Grants Awarded in 2011

Bertarelli Grants 2014
Through the generosity of the Bertarelli Foundation in Switzerland, a limited number of grants will be funded to support research projects in neuroengineering, with a focus on novel approaches to understanding or treating sensory disorders. To promote collaborations between Harvard and Swiss scientists, and collaborations between neuroscientists and engineers, each project must be carried out jointly by groups at Harvard and at the Ecole Polytechnique Fédérale de Lausanne.

This year, five projects will be funded with grants in the range of CHF630,000/$720,000 total per project, shared between HMS and EPFL. Applications are due by July 1, 2014 and decisions will be made in Summer, 2014. Funding will begin in January, 2015.

To read the requirements and format of proposal, download the Call for Applications.

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Harvard Medical School and Ecole Polytechnique Fédérale de Lausanne (EPFL) Launch Joint Program to Improve Quality of Life for People With Neurological Disabilities
$3.6 Million Grant from Bertarelli Foundation to Underwrite Cutting-Edge Research

(Boston, MA, October 24, 2011) Two of the world’s leading universities are joining forces to combine neuroscience and engineering in order to alleviate human suffering caused by such neurological disabilities as paralysis and deafness. Scientists, engineers, and clinicians at Harvard Medical School (HMS) and Ecole Polytechnique Fédérale de Lausanne (EPFL) will collaborate on six pioneering neuroengineering projects made possible thanks to a $3.6 million grant from the Bertarelli Foundation. Bringing together the best of U.S. medical science and Swiss bioengineering expertise, the researchers will employ the latest technologies in gene therapy, flexible electronics, optical imaging and human-machine interfaces to repair spinal injuries and hearing loss.

The collaboration launch will be celebrated at Harvard this weekend, the 28th and 29th of October, with a scientific symposium called “Neuroengineering Approaches to Sensory and Motor Disorders” that will bring together some of the world’s pioneers in the field.

“There have been huge advances in our basic understanding of the brain and the senses,” said David Corey, Director of the Bertarelli Program at Harvard Medical School, “but they have not been applied to neurological problems as quickly as we would like. This unique program will combine research advances in neuroscience with the special technologies and strategies of engineers, to speed new treatments to the clinic.”

“This is a unique chance to bring bioengineering solutions to clinical trials by combining HMS’s vast resources and skills at their university hospitals and EPFL’s distinctive combination of life science and engineering facilities,” says Patrick Aebischer, President of EPFL, one of Europe’s premiere universities for engineering, technology, and computer science.

Six Groundbreaking Research Projects in Translational Neuroscience

In five of the six inaugural research projects of the Bertarelli Program, basic scientists and physicians at HMS will be working with EPFL bioengineers to create new methods to diagnose and treat a wide range of hearing loss afflictions, from those that are genetically based to those caused by damage from excessive noise. A sixth project will build on novel research on spinal cord stimulation done in Switzerland, taking it a step further by implementing stretchable electronics directly on the spinal cord and attempting to rebuild severed connections through stem cell regeneration therapy.

Seeing how we hear

One of the great challenges in diagnosing hearing problems is that the physician cannot see the tissues and cells of the inner ear. In recent years, microendoscopes have been used experimentally to try to image the cells of the inner ear, but these rely on adding fluorescent dyes, something not practical for human diagnosis. At the same time, physicists have developed methods for imaging without dyes. For this project, a physicist from EPFL will collaborate with an HMS otologic surgeon to develop new imaging methods for the human inner ear. The researchers will use mouse and human inner ear tissue to optimize these new detection methods, learning, for instance, how to look through bone with long-wavelength light. Through imaging inner ear cells in animal models, they will set the stage for eventual clinical trials.

Konstantina Stankovic, Harvard / Mass. Eye & Ear Infirmary
Demetri Psaltis, EPFL

Gene therapy targets inherited deafness

About one in a thousand children are born with some form of hearing loss, often caused by inheritance of a mutant gene. For over ten years, researchers have looked to correct a variety of inherited disorders with gene therapy, a process in which genetically engineered viruses carry corrective genes into cells affected by a mutant gene. Some early failures diminished gene therapy’s promise, but new trials in humans have been remarkably successful and have raised hopes for conditions such as hearing disorders. A problem for gene therapy is that there are few viruses known to enter the inner ear’s sensory hair cells. A pioneer in use of viruses for hair-cell physiology from HMS and Children’s Hospital Boston and an EPFL expert in gene therapy for humans will collaborate to explore new viruses to carry genes into hair cells. Through restoring sensory cell function in mice with gene mutations that mimic human deafness, the researchers will attempt to correct inherited deafness in a live mouse. This research may clear a path for developing similar tools to restore hearing function in humans.

Jeffrey R. Holt, Harvard / Children's Hospital
Patrick Aebischer, EPFL

Treating deafness through regeneration

Much of the hearing loss that affects older people is caused by the death of sensory cells and neurons in the inner ear, a consequence of loud noise, infection, or certain drugs. This is often accompanied by tinnitus, an incessant sense of ringing in the ears. Unfortunately, these sensory cells do not regenerate they way skin or blood cells do. A first step in treating this hearing loss is to learn how to regenerate inner-ear sensory cells and neurons. Harvard scientists have recently learned how to isolate cells from a developing inner ear and to genetically reprogram them to proliferate into millions in a dish. The challenge now is to turn them into sensory cells and nerve cells. An HMS world expert in inner ear development will work closely with an exceptionally creative bioengineer from EPFL. By investigating molecular changes that occur in inner ear cells when they proliferate, and then using a micro-engineered screening platform to test thousands of compounds simultaneously, the researchers will seek to find factors that convert proliferating cells into hair cells or neurons. Finally, these factors will be tested in mice that are deaf from genetic or environmental causes.

Lisa Goodrich, Harvard Medical School
Matthias Lutolf, EPFL

Delivering drugs to treat hearing loss?

Once scientists learn to regenerate sensory cells in the laboratory, it is still a huge leap to make this happen in a human patient. The right drugs or chemical factors must be delivered to the inner ear, held in the right place, and released slowly over months, all without damaging the delicate sound-sensing structures. In this project, a pioneer in hair-cell regeneration from HMS will work with an EPFL bioengineer specializing protein engineering and nanotechnology techniques to develop new ways of delivering regenerative factors to the inner ear. Bound to hydrogels or packaged in novel "polymersomes” the factors will be taken up by the remaining cells, and will reprogram them to proliferate and morph into sensory cells.

Zheng-Yi Chen, Harvard / Massachusetts Eye & Ear Infirmary
Jeffrey Hubbell, EPFL / Institute of Bioengineering

New generation of auditory brainstem implants

The cochlear implant, a device that bypasses a damaged inner ear and conveys electrical signals directly to the auditory nerve, has been the most successful neural prosthesis of that past few decades, with over 200,000 in use worldwide. However a substantial fraction of patients are not candidates for a cochlear implant, and there has been great interest in developing a similar prosthesis that bypasses the damaged auditory nerve by directly stimulating the brainstem. But most attempts have failed, either because the electrodes inserted are not sufficiently flexible to conform to the neural tissue, or because the electrodes stimulate too broad a population of brainstem neurons. HMS specialists will investigate optical stimulation of the brainstem, using either intrinsic sensitivity to infrared light or modifying brainstem neurons to respond to blue light. EPFL will develop flexible electronics, combining electrical and optical stimulation, that conform to the contours of the brainstem and are easier to employ during surgery.

Daniel J. Lee and Christian Brown, Harvard / Mass. Eye & Ear Infirmary
Stéphanie P. Lacour, Philippe Renaud and Nicolas Grandjean, EPFL

Walking again

A complete spinal cord injury leaves a person paralyzed with no hope of recovery, because the brain can no longer send signals to body’s extremities. EPFL has already made groundbreaking research in spinal cord stimulation using electrodes and pharmaceutics to reawaken the dormant circuitry that controls the legs, allowing animals to walk again, but involuntarily. For this locomotion to become voluntary, signals must come from the brain. HMS is working on silencing two genes that could lead to the re-growth of the neural fibers severed in the accident, bridging the injury and re-establishing voluntary leg movement when coupled with stimulation.

Zhigang He and Clifford Woolf, HMS / Children's Hospital
Stéphanie P. Lacour and Grégoire Courtine, EPFL
The Bertarelli Program in Translational Neuroscience and Neuroengineering
The Bertarelli Program in Translational Neuroscience and Neuroengineering is a joint research and education program between Harvard Medical School and Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland to combine advances in basic neuroscience with engineering strategies and technologies, to improve the quality of life for people with neurological disabilities. The Program provides grants to support three-year collaborative research projects in neuroengineering, with a focus on novel approaches to understanding or treating sensory and motor disorders. To promote collaboration between U.S. and Swiss scientists, each project is carried out jointly by groups at Harvard Medical School and EPFL. The program was established in 2010 thanks to a generous commitment from the Bertarelli Foundation.

Harvard Medical School
Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School’s Boston campus or in one of 47 hospital-based clinical departments at 17 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Cambridge Health Alliance, Children’s Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children’s Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.

Ecole Polytechnique Fédérale de Lausanne (EPFL)
By combining the tradition of precision micro-technology in watch making with cutting-edge research in 21st century science, EPFL has become one of Europe’s leading technical universities—attracting top researchers and industrial partners from around the world. Logitech (an EPFL start-up beginning in the 1980’s), Nokia, Nestlé and Credit Suisse have set up R&D headquarters on campus, and many of its professors are counted among the best in their fields, making it one of the most important hubs for technology development in Europe. Taking its current form only at the end of the 1960s, EPFL leads some of Europe’s most daring projects: The Human Brain Project to simulate the human brain in a super-computer; TOBI, to develop non-invasive interfaces for disabled persons; The Steeper project, to reduce energy use ten-fold in computers; as well as other pioneering projects in the fields of medical imagery, neurosciences, robotics, computer science, transportation, and fundamental science.
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