Long-Term Contraception in a Single Shot

Caltech biologists have developed a nonsurgical method to deliver long-term contraception to both male and female animals with a single shot. The technique—so far used only in mice—holds promise as an alternative to spaying and neutering feral animals.

The approach was developed in the lab of Bruce Hay, professor of biology and biological engineering at Caltech, and is described in the October 5 issue of Current Biology. The lead author on the paper is postdoctoral scholar Juan Li.

Hay's team was inspired by work conducted in recent years by David Baltimore and others showing that an adeno-associated virus (AAV)—a small, harmless virus that is unable to replicate on its own, that has been useful in gene-therapy trials—can be used to deliver sequences of DNA to muscle cells, causing them to produce specific antibodies that are known to fight infectious diseases, such as HIV, malaria, and hepatitis C.

Li and her colleagues thought the same approach could be used to produce infertility. They used an AAV to deliver a gene that directs muscle cells to produce an antibody that neutralizes gonadotropin-releasing hormone (GnRH) in mice. GnRH is what the researchers refer to as a "master regulator of reproduction" in vertebrates—it stimulates the release of two hormones from the pituitary that promote the formation of eggs, sperm, and sex steroids. Without it, an animal is rendered infertile.

In the past, other teams have tried neutralizing GnRH through vaccination. However, the loss of fertility that was seen in those cases was often temporary. In the new study, Hay and his colleagues saw that the mice—both male and female—were unable to conceive after about two months, and the majority remained infertile for the remainder of their lives.

"Inhibiting GnRH is an ideal way to inhibit fertility and behaviors caused by sex steroids, such as aggression and territoriality," says Hay. He notes that in the study, his team also shows that female mice can be rendered infertile using a different antibody that targets a binding site for sperm on the egg. "This target is ideal when you want to inhibit fertility but want to leave the individual otherwise completely normal in terms of reproductive behaviors and hormonal cycling."

Hay's team has dubbed the new approach "vectored contraception" and says that there are many other proteins that are thought to be important for reproduction that might also be targeted by this technique.

The researchers are particularly excited about the possibility of replacing spay–neuter programs with single injections. "Spaying and neutering of animals to control fertility, unwanted behavior, and population numbers of feral animals is costly and time consuming, and therefore often doesn't happen," says Hay. "There is a strong desire in many parts of the world for quick, nonsurgical approaches to inhibiting fertility. We think vectored contraception provides such an approach."

As a next step, Hay's team is working with Bill Swanson, director of animal research at the Cincinnati Zoo's Center for Conservation and Research of Endangered Wildlife, to try this approach in female domestic cats. Swanson's team spends much of its time working to promote fertility in endangered cat species, but it is also interested in developing humane ways of managing populations of feral domestic cats through inhibition of fertility, as these animals are often otherwise trapped and euthanized.

Additional Caltech authors on the paper, "Vectored antibody gene delivery mediates long-term contraception," are Alejandra I. Olvera, Annie Moradian, Michael J. Sweredoski, and Sonja Hess. Omar S. Akbari is also a coauthor on the paper and is now at UC Riverside. Some of the work was completed in the Proteome Exploration Laboratory at Caltech, which is supported by the Gordon and Betty Moore Foundation, the Beckman Institute, and the National Institutes of Health. Olvera was supported by a Gates Millennium Scholar Award.

Writer: 
Kimm Fesenmaier
Writer: 
Exclude from News Hub: 
No
News Type: 
Research News

Capturing the Right Odors to Study the Brain

Hong and colleagues aim to reveal neural mechanisms related to olfaction

Over the summer, Betty Hong, assistant professor of neuroscience, spent a week at the Janelia Research Campus in Ashburn, Virginia, interacting and brainstorming with other researchers from around the country interested in olfaction, our sense of smell. Invited to participate by the National Science Foundation (NSF), these 30 computational and experimental neuroscientists came up with innovative ways to approach some of the mysteries about how the brain processes odors and uses that information to guide behavior.

The five-day session was an example of the agency's new funding mechanism, the Ideas Lab. At these meetings, a multidisciplinary group of researchers is charged with generating potentially transformative proposals on a focused research topic. Now the NSF has awarded $15 million to three projects from the Olfactory Ideas Lab. Hong is coprincipal investigator on one titled "Using natural odor stimuli to crack the olfactory code." The awards expand NSF's investments in President Obama's BRAIN Initiative.

"I am grateful to have had the opportunity to be thrown together for a week with such a smart, diverse group of scientists who approach olfaction from so many different angles," says Hong (BS '02), adding that without the Ideas Lab, it is unlikely that she would have ever established collaborations with her coinvestigators. "I am also extremely grateful to the NSF for including junior investigators like myself who are just kicking off their research program. This unique funding mechanism will enable us to tackle really challenging and innovative research right at the start of our careers."

Olfactory scientists typically use simple synthetic odors involving single molecules for their experiments because natural odors—those that we smell around us every day—are too difficult to reproduce in a reliable way under controlled conditions. However, those simplified stimuli may not trigger the full range of neural computations that constitute olfaction.

Therefore, Hong and her colleagues aim to use comprehensive chemical analysis and computational methods to construct reproducible synthetic odorants in the lab that mimic naturally occurring smells in terms of eliciting typical behavioral responses in honey bees, fruit flies, and fly larvae. (Hong specializes in studies of the fruit fly Drosophila.) These synthetic odor blends can then be used to investigate how the brain processes smells and orders specific adaptive behaviors.

"We believe probing the olfactory circuit with naturalistic stimuli will reveal long-hidden computational features of the circuit," Hong explains. "Much as higher-order visual neurons only respond to complex stimuli like faces or hands, and not to simple bars and dots, we hypothesize that naturalistic odor stimuli will reveal novel features of odor space that the olfactory system encodes, which may only become apparent once appropriate sets of stimuli are used."

Along with Hong, additional principal investigators on the project are Brian Smith of Arizona State University; Aravinthan Samuel of Harvard University; and Tatyana Sharpee of the Salk Institute for Biological Studies. The project will receive $3.6 million over three years.

Writer: 
Kimm Fesenmaier
Home Page Title: 
Capturing the Right Odors to Study the Brain
Writer: 
Exclude from News Hub: 
No
News Type: 
Research News
Exclude from Home Page: 

Summer Interns Return with a World of Experiences

Caltech undergraduate students returned to campus this week, many after spending the summer working at companies in biotechnology, technology, and finance, among other fields. These students have had the opportunity to learn firsthand about the career opportunities and paths that may be available to them after graduation. They also had the chance to put Caltech's rigorous academic and problem-solving training to the test.

In the summer of 2015, nearly a third of returning sophomores, juniors, and seniors were placed in an internship position through Caltech's Summer Undergraduate Internship Program (SUIP). The program, run through the Institute's Career Development Center (CDC), helps connect current undergraduate students with a wide range of companies and businesses that can provide practical skills and work experiences that give the students an edge in the future job market.

Many undergraduates find paid summer internships through the CDC, says Lauren Stolper, the director of fellowships, advising, study abroad, and the CDC. The center organizes fall and winter career fairs and offers workshops related to finding internships; provides individual advising on internship options and conducting a job hunt for an internship; organizes interviews for students through its on-campus recruiting program; and provides web-based internship listings and company information through Techerlink, its online job-posting system.

Through the formal establishment of SUIP two years ago—thanks, in part, to the initiative of Craig SanPietro (BS '68, engineering; MS '69, mechanical engineering) and with seed money provided by him and three of his alumni friends and former Dabney House roommates, Peter Cross (BS '68, engineering), Eric Garen (BS '68, engineering), and Charles Zeller (BS '68, engineering)—the CDC has been able to dedicate even more time and attention to helping undergraduates secure these important positions, Stolper says.

"Through internships, students have the opportunity to learn more about the practical applications of their knowledge by contributing to ongoing projects under the guidance of professionals," says Aneesha Akram, a career counselor for internship development/advising, who oversees SUIP.

"Completing summer internships help undergraduates become competitive candidates for full-time positions," says Akram. "When it comes to recruiting for full-time positions, companies seek out candidates with previous internship experience. We have found that many large companies extend return offers and full-time conversions to students who previously interned with them."

The infographic at the above right provides a snapshot of Caltech undergraduate internships over this past summer. Students seeking internships for next summer can contact Akram or look at the CDC website for more information.

Writer: 
Exclude from News Hub: 
No
Short Title: 
A World of Experiences
News Type: 
In Our Community
Thursday, October 1, 2015
Cahill, Hameetman Auditorium – Cahill Center for Astronomy and Astrophysics

Launch of Engineers Week at Caltech

Friday, October 23, 2015
Winnett Lounge – Winnett Student Center

Flat Space, Deep Learning: A Workshop by Eric Mazur

Wednesday, October 21, 2015
Beckman Institute Auditorium – Beckman Institute

The Teaching and Learning Project, a National Photographic Essay on Higher Education Featuring Caltech

Tuesday, October 20, 2015 to Wednesday, October 21, 2015
Center for Student Services 360 (Workshop Space) – Center for Student Services

Guest Consultations on Teaching, with Chris Duffy

Tuesday, October 20, 2015
Dabney Hall, Lounge – Dabney Hall

Bringing Joy into Your Teaching: A Workshop by Chris Duffy

Monday, October 19, 2015
Guggenheim 101 (Lees-Kubota Lecture Hall) – Guggenheim Aeronautical Laboratory

The Future of Teaching and Learning at Caltech: An Innovation Showcase

Monday, October 19, 2015 to Friday, October 23, 2015

TeachWeek Caltech

Pages