Associate Professor Brian Lawson, Ph.D. Antiretroviral therapy currently on the market is highly effective in the treatment of HIV, lowering viral loads and inhibiting disease progression; the problem is that these drugs do not affect dormant HIV hidden in host immune cells and, over time, are associated with significant toxicity. Therefore, how do we completely eliminate HIV, active and latent, from an infected person? One exciting approach to achieve that goal is the use of chimeric antigen receptor (CAR) T cell immunotherapy, which gained broad recognition as a new treatment modality for certain blood cancers. CAR T cells are derived from a patient’s own cells, and are engineered to identify and kill specific target cells. These T cells are especially suited to finding and killing cells that express very low levels of target proteins. Moreover, their self-sustaining nature and ability to traffic and surveil virtually the entire host are highly beneficial aspects for controlling a chronic systemic pathogen such as HIV. Indeed, in recent unrelated cancer trials, functional CAR T cells were documented in many purported HIV sanctuary sites, including the central nervous system, the digestive tract, genital tracts, secondary lymphoid tissues, etc. CAR T cells can safely stay in humans for a surprising length of time (>16 years), and thus could be excellent and safe platforms to act as long-term anti-viral sentinels. Continue reading

SURE Program 2022
"It's a wrap!" - Scintillon's summer high school student research program excites young minds and comes to an end for 2022. Every year, Scintillon’s research faculty perform exciting biomedical research pushing for a cure of many major disease conditions, including neuroscience, immunology, virology, and aging-associated diseases. Towards these ends, the faculty has to secure new grants and new philanthropy to resource these efforts. In addition to these difficult challenges, every summer the faculty also joins together and donates a significant amount of their time and effort to teach and host a growing number of very highly motivated local San Diego high school students in Scintillon’s research laboratories for an intensive 4-week training program. The small number of high school students accepted into the highly-competitive program are some of the highest performing students in the entire county, and past alumni of the program have, not surprisingly, gone on to attend elite universities, including Dartmouth, Johns-Hopkins, Stanford, and Yale. This year’s SUmmer REsearch (SURE) program had its highest number of applicants to date—twice as many as last year. While that is great news for the program, we at Scintillon had to use every possible resource at our young Institute to accept and serve this class of 2022, the largest class in our 5-year program’s history. It wasn’t easy! Continue reading

This protein can help us think. Or it can shred our cells.
San Diego – A new study reveals that a protein long known to play a role in communication between cells in the brain is also capable of obliterating cells if left unchecked because of its penchant for twisting and puncturing the cell membranes. The protein — known as complexin — if left alone is so toxic it can shred cells. Yet, in the brain, a suite of controls makes sure the protein plays nice and helps neurons communicate by aiding in the release of neurotransmitters. The findings are published Feb. 7 in Nature Structural and Molecular Biology. "We argue that’s the most interesting membrane fusion event in our bodies, because it’s the one that underlies this conversation. It controls remembering and forgetting. It is everything," says Ed Chapman, professor of neuroscience at the University of Wisconsin School of Medicine and Public Health. "Yet to this day, nobody knows just how the proteins involved in this process really work." In trying to better understand these proteins Chapman's lab and their collaborators discovered the surprising power of complexin. They found that it dramatically bends and reorders membranes. Live videos show the protein pinching off small bubbles of membrane while simultaneously poking holes in them.  Ultrahigh-resolution 3D images produced by the laboratories of Dorit Hanein and Niels Volkmann at the Scintillon Institute in San Diego also revealed, directly through Cryo-EM imaging, that complexin induces the formation of twisting curlicues of broken-apart membranes. Continue reading

International Conference on Three-dimensional Cryo-EM Image Analysis
The 4th International Conference on Three-dimensional Cryo-EM Image Analysis will be held March 9-12, 2022, at Granlibakken Conference Center, Lake Tahoe, California. The 2022 conference builds on our successful previous events on the same theme in 2014, 2016 and 2018. This year the conference is organized by Scintillon Professors Dorit Hanein and Niels Volkmann.The goal of this series of meetings is for technical discussions of state-of-the-art image analysis approaches and algorithm developments to tackle challenging biological problems and to identify current limitations in the field. We have recruited an outstanding panel of speakers with topics at the 2022 meeting to include: tomography and high resolution subtomogram averaging, conformational variability, deep learning, model-based refinement, and automation.  In addition, there will be a dedicated session for selected poster talks.  All sessions will focus on interactive discussions with plenty of time for questions. The preliminary program and registration details can be found at Dorit Hanein, CHAIR & Steven Ludtke, Co-CHAIRORGANIZING COMMITTEE: Masahide Kikkawa,  Jose Maria Carazo, Scott Stagg, Niels Volkmann, Ed Egelman

Recent advances in structural biology research by Scintillon researchers
Rapid tool for cell nanoarchitecture integrity assessment Detailed three-dimensional contextual information of molecular processes is often necessary to understand these processes well enough to develop efficient drug-targeting and disease intervention strategies in all medical fields. We developed a tool that significantly accelerates studies providing such information (Gaietta et al., 2021 Journal of Structural Biology). Structural basis of aE-catenin–F-actin catch bond behavior A better understanding of how cell-cell contacts are maintained or broken is essential for unraveling the detailed mechanism of cancer progression. For example, cells need to detach to become metastatic and need to maintain contacts within a tumor. Our study significantly deepened our understanding of how cell-cell contacts work and thus potentially opens new opportunities for medical intervention in cancer progression (Xu et al., 2020 eLife). The actomyosin interface contains an evolutionary conserved core and an ancillary interface involved in specificity The knowledge obtained in our study has direct impact on drug-targeting strategies for malaria by telling researchers which regions of the interface are promising targets for disrupting the function of the malaria proteins while, at the same time, minimizing the potential of disrupting human protein interaction, thus preventing potential side effects (Robert-Paganin et al., 2021 Nature Communications). Continue reading

A brain network that curbs the urge to eat
Scintillon Institute researchers uncover an evolutionarily conserved brain region that puts a “brake” on food intake which may advance therapeutics for obesity and related disorders with excessive eating such as Prader-Willi syndrome. Do you ever wonder why you stop eating even when there are appealing foods available? The cerebellum compares hunger state with after-eating nutritional status in the gut to regulate dopamine reward signals in the striatum to control meal size. click here for higher-res image credit: Aloysius Y. T. Low A multi-institution collaboration led by Associate Professor Albert I. Chen at the Scintillon Institute, Assistant Professor J. Nicholas Betley and Postdoctoral Fellow Aloysius Low at the University of Pennsylvania searched for brain regions that might provide a stop signal for feeding and identified the cerebellum, a brain region outside of the conventional feeding network, as an important regulator of meal size. Neural activity of this region directs the suppression of food intake in mice, and this activity is abolished in human subjects with insatiable appetite. Their findings were published in the journal Nature on November 17, 2021. Continue reading

Scintillon Institute Investigator Awarded NIH R35 Early-Career Grant
Metabolism or the set of life-sustaining chemical reactions defines the very wellbeing of humans. But can we better understand how cellular metabolism goes awry in various human diseases? The National Institute of General Medical Sciences just granted Scintillon’s Dr. Valentin Cracan $2.4 million to find out more! The National Institute of General Medical Sciences (NIGMS) has recognized Dr. Valentin Cracan as one of the nation’s highly talented and promising scientists to receive a Maximizing Investigators’ Research Award for Early-Stage Investigators (R35 MIRA-ESI).  This grant provides about $2.4 million over five years to support the ongoing work at the Cracan’s lab that has received a number of NIH grants already since it was established about 3 years ago. We spoke with Valentin as we were interested in his research in the context of his new, special grant.    PATH TO SCINTILLON Valentin received his undergraduate degree in Biology and Biochemistry from the Moldova State University in the Republic of Moldova in 2005 and his Ph.D. in Biological Chemistry from University of Michigan in 2012, where he studied the intracellular pathway for trafficking of vitamin B12 (cobalamin) in the laboratory of Professor Ruma Banerjee.  While in graduate school, Valentin significantly contributed to our understanding of vitamin B12-dependent cell metabolism. In 2012, he joined the laboratory of Professor Vamsi Mootha at the Massachusetts General Hospital and Harvard Medical School. There, he obtained further training in studying mitochondria, the energy factories of our cells and major hubs of cellular metabolism. In the winter of 2018, Valentin joined the Scintillon Institute faculty as an Assistant Professor. Continue reading

Does science save lives during this pandemic?
  - Did science save lives during this pandemic that we are still in? - Are Biomedical and Bioengineering Sciences interesting and important subjects?    “Yes!” many of today’s high school students will say that without hesitation.  But is science research a field where you want to build a career? Many students may still want to say “Yes…” but maybe blindly.   Scintillon Institute, a premium San Diego research institution for nonprofit purposes, has built its now famous Scintillon “SURE” (SUmmer REsearch) program to help top-performing high school students to find out for themselves whether conducting scientific research and becoming a career scientist is for them.  Continue reading

A New Twist in the Tale of Experimental Immunotherapies for Parkinson’s Disease
A new study co-led by Scintillon Institute’s Associate Professor, Dr. Rajesh Ambasudhan, and Adjunct Professor Dr. Stuart Lipton (also a practicing Neurologist at UC San Diego) shows that certain immunotherapy approaches for Parkinson’s disease (PD) may cause harmful neuroinflammation by activating microglia (brain’s immune cells) and that this adverse effect could offset therapeutic benefits elicited by the antibody treatment. The study appeared in the April 13, 2021 issue of the Proceedings of the National Academy of Science of the United States of America. Continue reading

Celebrating Scintillon wins in early 2021
The Scintillon Institute is proud to announce the recent addition to its faculty, Dr. Albert Chen, a neurobiologist who specializes in examining the link between neural circuits and behavior in health and disease.  Albert Chen joins Scintillon Institute as an Associate Professor of Neuroscience after spending eight years at the Nanyang Technological University in Singapore. Research in his lab employs a multidisciplinary approach to define the molecular, anatomical, and functional distinctions of brain centers important for coordination and refinement of movement, motor learning, and complex motivated behaviors using genetic and viral circuit tracing, neural manipulations, deep brain imaging and quantitative behavioral approaches in mice. The rising prevalence of obesity and eating disorders is a significant public health crisis, and dysfunctions of subcortical and hindbrain networks important for feeding behaviors and metabolism have been implicated. With a recently awarded R01 from the NIH, an exciting new project in the Chen lab aims to identify and characterize previously unknown components of the neural network that mediates food seeking and consumption, with a long-term goal of exploring the efficacy of drugs and brain stimulation as effective therapeutics for body weight control. Continue reading