NIH Grants and a Collaboration with Caltech Provide new Research Opportunities

COLLABORATION WITH CALTECH

An exciting collaboration with Caltech’s CLOVER Center will train CPP students to develop and disseminate tools to the neuroscientific community that will allow for monitoring and manipulating neuronal cells across vertebrate species.

This project will pair the NIH-funded AAV BRAIN Safe and Effective Neuromodulator and Sensor Utilization across Species (SENSUS, led by Caltech) with CPP to build a new Armamentarium Vector Core (ArmVC), broadening the Armamentarium project’s ability to validate and disseminate the next generation of modern gene delivery tools to understand and, eventually, treat the brain[1].

Engineered Adeno-Associated Virus (AAV) strains are desirable as vectors in gene therapy due to their ability to cross the blood-brain barrier. They are safe because they can’t replicate. There’s no risk of infection.

The program is called the AAV Brain SENSUS Program for Inclusive Research Experiences (ASPIRE). Under the supervision of CPP Professor Andrew Steele, ASPIRE students will receive training from Caltech experts in AAV engineering for neuroscience that will increase their career readiness.

“We’re investigating which cell types the AAV targets. It’s interesting research with the potential for developments in medicine.” said CPP student Fernando Garcia. “This experience through the Steele lab has taught me to analyze situations at a deeper level and expand my critical thinking skills.” Skills that will serve Garcia well in his goal to become a doctor.

Students will use immunohistochemistry to independently validate novel AAV produced at Caltech. They will also produce validated AAV and disseminate them through the ArmVC at CPP, making these valuable tools available to other researchers. “We already have preorders,” Steele said.

ASPIRE students will also attend workshops, research seminars, make poster presentations, and attend career-focused mentoring meetings with Caltech Principal Investigator Viviana Gradinaru, Ph.D.

Alumnus (’17, B.S. in biology, ’19, M.S. in biology) and former Steele lab member Damien Wolfe is the program manager and research technician at the CLOVER Center. He is the liaison between Caltech and CPP and is teaching students the theory and skills involved in AAV engineering.

“I've always had a passion for both science and teaching, so this program was the perfect opportunity for me to take all of the mastery I have acquired and pass that on to the next generation of scientists,” Wolfe said. “With the leadership of Dr. Steele and Dr. Timothy Shay at Caltech, we are looking forward to giving students, especially those who are underrepresented, an opportunity to do high-level research.”

“I had research experiences at CPP that gave me a foundation in the field of biology,” Wolfe said. “I did plant genetics research with Dr. Sharma and neuroscience research with Dr. Steele which was invaluable and prepared me for my current job. I wouldn’t be where I am without it.”

[1] From the Public Health Relevance Statement of the Project Narrative.

NIH GRANTS FUND EATING AND OBESITY RESEARCH 

Professor Steele is principal investigator on two NIH grants. One seeks to identify the neurons in the brain that regulate the timing of feeding and their connection to circadian rhythms and food anticipatory activity in mice.

The second will explore the underlying mechanisms of eating for pleasure and will test the hypothesis that “dopaminergic input from a select group of VTA-DA neurons to the suprachiasmatic nucleus (SCN) is an integral part of the hedonic feeding neurocircuitry,” the grant proposal states.

Obesity in the United States is an ongoing problem that contributes to the development of a number of diseases such as cardiovascular disease, cancer, and diabetes. The National Institute of Diabetes and Digestive Kidney Disease, which is funding this research, states that more than 2 in 5 adults (42.4%) have obesity (including severe obesity).

A study funded by the National Heart Lung and Blood Institute found that American’s bad eating habits result in $50 billion in health care costs. Every year an estimated 45 million Americans try dieting and spend over $30 billion on weight loss products.

A better understanding of the neurological processes of reward-based eating may help us to develop effective solutions to diet-induced obesity. Steele’s lab is also studying the connection of neurological processes to the time of eating because it affects body weight homeostasis.

As Steele describes, “Mice normally consume most of their food at night. When switched to a high fat diet they consume more calories during the day. Mice with specific dopamine receptors knocked out didn’t increase day eating and though they ate the same high fat food, they didn’t gain weight.” Steele cautions that, “The knockout mice may have elevated metabolisms that’s causing that effect so we’re working with Western University to measure metabolism too.” 

In humans, who are normally day eaters, this research could possibly lead to techniques for silencing the neurons that would constrain night eating.

Students are gaining valuable skills in Steele’s lab. Senior Luis Rivera said he’s learned how to prepare a brain for antibody staining. It involves collecting mouse brain tissue, preserving it, then sectioning it with a vibratome so they can stain it with molecular probes. “This is one of the most interesting and crucial steps in the research as it helps us visualize the composition of the target strain and its overall expression of dopamine,” Rivera said. 

Rivera plans to become a medical doctor. He said, “This experience has taught me to follow protocol and work as a team, also to increase my work pace and avoid errors under pressure.”

Graduate student Jason Lee, who trains new students in Steele’s lab on basic skills, said, “My original career goal was to become a dentist, but I discovered my passion for research and learning about the brain.” He plans to pursue a Ph.D. in neuroscience and work for a biotech company. “The lab techniques I learned working with Dr. Steele mentally and physically trained me to be a good scientist and has prepared me for my future."