Enhancer elements in the human genome control how genes are expressed in specific cell types and harbor thousands of genetic variants that influence risk for common diseases. Yet, we still do not know how enhancers regulate specific genes, and we lack general rules to predict enhancer–gene connections across cell types. We developed an experimental approach, CRISPRi-FlowFISH, to perturb enhancers in…
Human iPSC-derived kidney organoids have the potential to revolutionize discovery, but assessing their consistency and reproducibility across iPSC lines, and reducing the generation of off-target cells remain an open challenge. Here, we profile four human iPSC lines for a total of 450,118 single cells to show how organoid composition and development are comparable to human fetal and adult kidneys. Although…
Active amplification of organized synaptic inputs in dendrites can endow individual neurons with the ability to perform complex computations. However, whether dendrites in behaving animals perform independent local computations is not known. Such activity may be particularly important for complex behavior, where neurons integrate multiple streams of information. Head-restrained imaging has yielded important insights into cellular and circuit function, but…
Read the Publication This week we profile a recent publication in Nature Protocols from Dr. Pierpaolo Peruzzi (pictured, third from left) with his lab at Brigham and Women’s Hospital. Can you provide a brief overview of your lab’s current research focus? We are interested in exploring the yet untapped features of non-coding RNA biology and harness them to develop a…
To make appropriate decisions, animals need to accumulate sensory evidence. Simple integrator models can explain many aspects of such behavior, but how the underlying computations are mechanistically implemented in the brain remains poorly understood. Here we approach this problem by adapting the random-dot motion discrimination paradigm, classically used in primate studies, to larval zebrafish. Using their innate optomotor response as…
Mucosal immunology research continues its fascination with microbial metabolites. In 2019, researchers uncovered extended functions for microbial metabolites in immunity, deepening our understanding of the regulation and function of metabolite-reactive immune cells, and revealed the receptors by which immune cells can recognize bioactive microbial metabolites.
Obesity is considered a strong factor in many chronic diseases, including heart disease, diabetes, and cancer. Along with genetics, consumption of excessive fat and cholesterol-rich food are the primary causes of obesity. We have developed an ionic liquid that interacts with fat to form micrometer-sized particles. The ionic liquid prevents the fat from penetrating through the intestinal membrane. We have…
Microglia, the resident immune cells of the brain, are known to be crucial for normal brain function as well as contributing to neurodegenerative disease. However, microglial cells are very sensitive to culture conditions and have been shown to lose their key properties when grown in vitro. In this study, we developed a model in which we transplant immature microglial cells…
The engineered AAV-PHP.B family of adeno-associated virus efficiently delivers genes throughout the mouse central nervous system. To guide their application across disease models, and to inspire the development of translational gene therapy vectors for targeting neurological diseases in humans, we sought to elucidate the host factors responsible for the CNS tropism of the AAV-PHP.B vectors. Leveraging CNS tropism differences across…
The current need for novel antibiotics is especially acute for drug-resistant Gram-negative pathogens. These microorganisms have a highly restrictive permeability barrier, which limits the penetration of most compounds. As a result, the last class of antibiotics acting against Gram-negative bacteria was developed in the 1960s. We reason that useful compounds can be found in bacteria that share similar requirements for…