New iBiology Videos Explore the Link Between Discovery and Medicine

“Interest in biology has never been higher,” says Louis Reichardt, emeritus professor of physiology at University of California, San Francisco (UCSF). And yet, as federal research funding declines, Reichardt worries that many graduate students are despairing of their prospects for productive research careers. “It takes some ingenuity now to find future opportunities in science,” he says. In recent years, Reichardt has devoted his own ingenuity to helping students find these opportunities. A glimpse of his work can now be seen on iBiology.org.

Reichardt knows something about training young scientists. He directed UCSF’s neuroscience graduate program for 25 years before retiring last year to become Director of the Autism Research Initiative at the Simons Foundation in New York. Five years ago, Reichardt decided that one way to improve career outcomes for his students would be to give them more exposure to connections between basic biology and medical applications. Increasingly, many of the opportunities for young biologists will be in clinical departments or the biomedical industry, Reichardt believes, but it hasn’t always been easy for graduate students to learn about the potential clinical applications of basic research.

So in 2009 Reichardt founded the Graduate Education in Medical Science (GEMS) program at UCSF, which offers training and financial support to students from any biomedical discipline interested in combining basic and clinical research. One of the pillars of the GEMS program is a series of evening lectures that pair basic scientists and clinicians to discuss connections between their research. Since their inception, the GEMS seminars have been popular with UCSF students and postdocs at many stages of their careers. Now aspiring scientists everywhere can tune in as well.

iBiology, the UCSF-based online video platform, began recording a series of GEMS-sponsored Bench to Bedside seminars with funding from the Howard Hughes Medical Institute and UCSF Medical School. Since June, six have been posted on the iBiology site, and more are in the works. “Often you only hear about the basic research discoveries that have not yet been medically applied or about mechanisms of drugs that have already been effective enough to be in clinical trials,” says iBiology Director Sarah Goodwin. “Rarely do you get to hear the start-to-finish story about how research in model organisms or cell lines turns into an effective treatment for a human disease.”

There’s Something about Cilia

One pair of videos — featuring UCSF faculty Wallace Marshall, professor of biochemistry and biophysics, and Jackie Duncan, professor of clinical ophthalmology — epitomizes how medical breakthroughs can blossom from the basic scientific desire to understand a puzzling anomaly.

In his talk, Marshall describes the strange history of the primary cilium, a microscopic, hair-like protrusion found on nearly every cell in the body. For a hundred years after its discovery in 1898, scientists assumed the primary cilium was an evolutionary or developmental relic, the cellular equivalent of the vestigial human tail-bone. Then, at the dawn of the 21st century, basic researchers studying the lowly alga, Chlamydomonas reinhardtii made two big discoveries that brought the primary cilium into the medical spotlight. First, they found a single genetic mutation that could completely eliminate cilia from the alga by messing up a transport protein needed to build these structures. Second, they realized a homolog, or analgous version of this gene, also existed in mice and humans. In mice, mutating the gene was fatal—pups died of polycystic kidney disease (PKD) soon after birth. The scientists examined kidney cells from these mice and found that they too lacked cilia.

Duncan takes up the story, describing how defective cilia were soon being implicated in all kinds of human disease. Duncan discusses how defective cilia produce syndromic disorders, now called ciliopathies, that affect organs across the body. When primary cilia are defective, the retina’s normally light-sensitive photoreceptors cease to function properly and may transform into fluid-filled cysts. The brain’s developing cerebellum may wind up deformed, leading to movement disorders. Ciliopathies can even cause the heart to form on the wrong side of the body or the growth of extra fingers and toes. Fortunately, says Duncan, our growing understanding of the genetics behind primary cilia defects has given clinical researchers a host of targets to hit with new therapeutics, offering hope of one day treating and preventing these diseases.

Here’s Drugs in your Eye

Another video in the GEMS iBiology series explores an ongoing UCSF collaboration to create transparent, foldable, biodegradable drug delivery devices that can be directly injected into the eyeball to treat diseases that cause blindness.

First, UCSF clinical ophthalmology professor Robert Bhisitkhul describes how research into vascular growth factors led to the development of new drugs that can help treat age-related macular degeneration, a leading cause of blindness in the elderly. Unfortunately, says Bhisitkhul, to be effective these drugs must be injected into the eye every month for up to two years, a procedure that is about as uncomfortable as it sounds.

In the second half of the talk, UCSF bioengineering professor Tejal Desai describes how her group collaborated with Bhisitkhul to engineer a high-tech replacement for these frequent, painful drug injections.

The seed of this collaboration was planted several years ago, Desai recalls, when Bhisitkhul heard her talk at a UCSF symposium on her lab’s efforts to engineer materials for drug delivery devices that could be injected under the skin or into muscles. Inspired, Bhisitkhul approached Desai at the post-talk reception and, over hors d’oeuvres, the two scientists began plotting better drug delivery systems for the eye.

Since then, Desai’s group has engineered a transparent, biodegradable device made out of a honeycomb-like material that could be flexible enough to be rolled up into a needle for injection but also robust enough to deliver a stable, carefully calibrated dose of drug over many months. She hopes to begin testing it for use in humans in the near future.

Desai says the interdisciplinary nature of UCSF and the chance for collaborations with clinicians like Bhisitkhul was one of the major reasons she decided to set up her lab there. “I could be a bioengineer, but could address a whole range of problems in medicine, in pharmacy, dentistry or basic science, just being surrounded by different people in different perspectives,” she said. “It’s not the conventional engineering department.”

This collaborative, solution-oriented spirit animates the whole GEMS iBiology series, which continues with one amazing tale after another of how basic biological research can lead to major advances in medical understanding.

For his part, Reichardt hopes that the GEMS Bench to Bedside series will encourage young researchers around the world. “My hope is that it just sort of inspires people to stay in science to know how much opportunity is out there, how much there is that remains to be discovered.”