DIBS Announces 2021-2022 Germinator Awards

Michael Adoff, Department of Neurosurgery

Development of a Functional Imaging Platform for Investigating Human Epileptic Neural Circuits

Almost 40% percent of people with epilepsy experience seizures that are uncontrolled by medications. Thus, there is an urgent need for development of new treatment options. Despite significant focus and investment on preclinical research using animal models, the proportion of patients with drug-resistant epilepsy has remained constant over the past 40 years, indicating the strong need for better ways of studying epilepsy and developing new types of therapies for it. To advance beyond the use of cell cultures and laboratory animals, which incompletely model human epilepsy, We are performing epilepsy research using human brain tissue derived from epilepsy neurosurgical procedures. This approach enables us to study the physiological mechanisms underlying human seizures in a system that embodies key features of human epilepsy. Our goal is to pair this model with advanced optical imaging methods that will allow us to understand human seizure initiation and spread at local (single cell) and global (whole epileptic network) levels. This platform will enable our lab and other researchers to develop novel epilepsy treatments in an exceptionally relevant system, ultimately accelerating and potentiating treatments for this challenging condition.

Hala El-Nahal, Biomedical Engineering

Marc Sommer, Biomedical Engineering

Building on Viral Advances in Macaques to Probe Circuit-Level Functions of the Claustrum

One of the least understood parts of the brain is the claustrum, a thin sheet of nerve cells under the cerebral cortex. The claustrum is difficult to target with electrodes or other classical neuroscience tools, so its functions remain elusive. Recently developed genetic techniques, however, provide new hope for understanding it. Microbial genes, called opsins, can be put into mammalian neurons to allow researchers to activate or inhibit them with light, an approach called optogenetics. In rodents, optogenetics has worked well for studying the claustrum, but in rhesus monkeys – the lab animal closest to humans – there has been no progress. This is because the only practical way of delivering genes to monkey neurons is using viruses, but currently available viruses are often unreliable. Our preliminary data suggests that a newly developed virus called rAAV2-retro is effective at delivering genes to the monkey claustrum. We aim to test rAAV2-retro as a means of performing optogenetics in the claustrum of monkeys. Specifically, we will investigate claustrum neurons that project to an area of the frontal lobe with a well-established role in attention. The results will enable a range of new investigations into the primate claustrum and tell us how claustrum dysfunction might contribute to brain disorders.

Maria Panzetta, Molecular Genetics & Microbiology

Raphael Valdivia, Molecular Genetics & Microbiology

William Wetsel, Psychiatry & Behavioral Sciences

Richard Bedlack, Neurology

Akkermansia Muciniphila in the Progression of Amyotrophic Lateral Sclerosis Disease

Trillions of microbes, collectively known as the microbiome, live in our gut. Perturbations to the gut microbiome can cause metabolic and inflammatory diseases. Transferring gut microbes from patients with obesity, autism, depression, and multiple sclerosis into mice often causes the same disease in the mice. Amyotrophic lateral sclerosis (ALS), is another illness that involves changes to the gut microbiome. We are interested in understanding how the microbiome influences ALS and identifying which bacteria impact the progression of the disease. One of the “good bacteria” in the gut microbiome, Akkermansia muciniphila (Am), alleviates ALS symptoms in mice. Using advanced techniques in microbiology, genetics, and metabolomics, we will identify which natural strains of Am and other bacterial species are most beneficial.  We will also define how Am in the gut impacts the onset of ALS. Findings from this work could uncover novel bacterial strains that protect from ALS and support the design of microbiome-based interventions to help people with ALS improve their quality of life. 

Allie Schrock, Evolutionary Anthropology

Christine Drea, Evolutionary Anthropology

Sex Steroid Receptor Distribution Across Lemur Brains in Relation to Social Dominance

In most social mammals, males are more aggressive than females.  However in some species, females instead show pronounced aggression towards males. Sex hormones, such as testosterone and estradiol, may play a role in this unusual phenomenon. Lemurs are a unique group in which to study these brain differences, because they show great variation in their social systems and male/female dominance patterns. At the Duke Lemur Center, we will study the brains of animals that died of natural causes to map hormone receptors in species that show a spectrum of female aggression, from being egalitarian to extremely aggressive towards males. Using state-of-the-art genetic techniques applied to brain sections, we will describe the location and quantify the number of sex hormone receptors in males and females of each species. For this study, we will focus on certain brain areas that differ between males and females and play a role in social behavior. These results will add to our knowledge of the relationship between hormones in the brain and female aggression, and shed light on human health conditions in which females are exposed to excessive sex hormones.