Bar Harbor, ME, United States

Howard Hughes Medical Institute

www.hhmi.org/
Bar Harbor, ME, United States

The Howard Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United States. HHMI spends about $1 million per HHMI Investigator per year, which amounts to annual investment in biomedical research of about $825 million. The institute has an endowment of $16.9 billion, making it the second-wealthiest philanthropic organization in the United States and the second best endowed medical research foundation in the world. HHMI is the former owner of the Hughes Aircraft Company - an American aerospace firm which was divested to various firms over time. Wikipedia.

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Sternson S.M.,Howard Hughes Medical Institute
Neuron | Year: 2013

Neural processes that direct an animal's actions toward environmental goals are critical elements for understanding behavior. The hypothalamus is closely associated with motivated behaviors required for survival and reproduction. Intense feeding, drinking, aggressive, and sexual behaviors can be produced by a simple neuronal stimulus applied to discrete hypothalamic regions. What can these "evoked behaviors"teach us about the neural processes that determine behavioral intent and intensity? Small populations of neurons sufficient to evoke a complex motivated behavior may be used as entry points to identify circuits that energize and direct behavior to specific goals. Here, I review recent applications of molecular genetic, optogenetic, and pharmacogenetic approaches that overcome previous limitations for analyzing anatomically complex hypothalamic circuits and their interactions with the rest of the brain. These new tools have the potential to bridge the gaps between neurobiological and psychological thinking about the mechanisms of complex motivated behavior. © 2013 Elsevier Inc.


Sudhof T.C.,Howard Hughes Medical Institute
Neuron | Year: 2012

Neurotransmitters are released by synaptic vesicle exocytosis at the active zone of a presynaptic nerve terminal. In this review, I discuss the molecular composition and function of the active zone. Active zones are composed of an evolutionarily conserved protein complex containing as core constituents RIM, Munc13, RIM-BP, α-liprin, and ELKS proteins. This complex docks and primes synaptic vesicles for exocytosis, recruits Ca 2+ channels to the site of exocytosis, and positions the active zone exactly opposite to postsynaptic specializations via transsynaptic cell-adhesion molecules. Moreover, this complex mediates short- and long-term plasticity in response to bursts of action potentials, thus critically contributing to the computational power of a synapse. © 2012 Elsevier Inc.


Anderson D.J.,Howard Hughes Medical Institute
Nature Reviews Neuroscience | Year: 2016

Goal-directed social behaviours such as mating and fighting are associated with scalable and persistent internal states of emotion, motivation, arousal or drive. How those internal states are encoded and coupled to behavioural decision making and action selection is not clear. Recent studies in Drosophila melanogaster and mice have identified circuit nodes that have causal roles in the control of innate social behaviours. Remarkably, in both species, these relatively small groups of neurons can influence both aggression and mating, and also play a part in the encoding of internal states that promote these social behaviours. These similarities may be superficial and coincidental, or may reflect conserved or analogous neural circuit modules for the control of social behaviours in flies and mice. © 2016 Macmillan Publishers Limited, part of Springer Nature.


Cepko C.,Howard Hughes Medical Institute
Nature Reviews Neuroscience | Year: 2014

Lineage studies conducted in the retina more than 25 years ago demonstrated the multipotency of retinal progenitor cells (RPCs). The number and types of cells produced by individual RPCs, even from a single time point in development, were found to be highly variable. This raised the question of whether this variability was due to intrinsic differences among RPCs or to extrinsic and/or stochastic effects on equivalent RPCs or their progeny. Newer lineage studies that have made use of molecular markers of RPCs, retrovirus-mediated lineage analyses of specific RPCs and live imaging have begun to provide answers to this question. RPCs that produce two postmitotic daughter cells-that is, terminally dividing RPCs-have been the most well characterized RPCs to date, and have been shown to produce specific types of daughter cells. In addition, recent studies have begun to shed light on the mechanisms that drive the temporal order in which retinal cells are born. © 2014 Macmillan Publishers Limited. All rights reserved.


Hudspeth A.J.,Howard Hughes Medical Institute
Nature Reviews Neuroscience | Year: 2014

Uniquely among human senses, hearing is not simply a passive response to stimulation. Our auditory system is instead enhanced by an active process in cochlear hair cells that amplifies acoustic signals several hundred-fold, sharpens frequency selectivity and broadens the ear's dynamic range. Active motility of the mechanoreceptive hair bundles underlies the active process in amphibians and some reptiles; in mammals, this mechanism operates in conjunction with prestin-based somatic motility. Both individual hair bundles and the cochlea as a whole operate near a dynamical instability, the Hopf bifurcation, which accounts for the cardinal features of the active process. © 2014 Macmillan Publishers Limited. All rights reserved.


Sudhof T.C.,Howard Hughes Medical Institute
Neuron | Year: 2013

Neurotransmitter Release: The Last Millisecond in the Life of a Synaptic Vesicle


Darnell R.B.,Howard Hughes Medical Institute
Annual Review of Neuroscience | Year: 2013

Neurons have their own systems for regulating RNA. Several multigene families encode RNA binding proteins (RNABPs) that are uniquely expressed in neurons, including the well-known neuron-specific markers ELAV and NeuN and the disease antigen NOVA. New technologies have emerged in recent years to assess the function of these proteins in vivo, and the answers are yielding insights into how and why neurons may regulate RNA in special ways-to increase cellular complexity, to localize messenger RNA (mRNA) spatially, and to regulate their expression in response to synaptic stimuli. The functions of such restricted neuronal proteins are likely to be complemented by more widely expressed RNABPs that may themselves have developed specialized functions in neurons, including Argonaute/microRNAs (miRNAs). Here we review what is known about such RNABPs and explore the potential biologic and neurologic significance of neuronal RNA regulatory systems. Copyright ©2013 by Annual Reviews. All rights reserved.


Lee S.H.,Howard Hughes Medical Institute
Neuron | Year: 2012

Switches between different behavioral states of the animal are associated with prominent changes in global brain activity, between sleep and wakefulness or from inattentive to vigilant states. What mechanisms control brain states, and what are the functions of the different states? Here we summarize current understanding of the key neural circuits involved in regulating brain states, with a particular emphasis on the subcortical neuromodulatory systems. At the functional level, arousal and attention can greatly enhance sensory processing, whereas sleep and quiet wakefulness may facilitate learning and memory. Several new techniques developed over the past decade promise great advances in our understanding of the neural control and function of different brain states. Copyright © 2012 Elsevier Inc. All rights reserved.


Stern D.L.,Howard Hughes Medical Institute
Nature Reviews Genetics | Year: 2013

The evolution of phenotypic similarities between species, known as convergence, illustrates that populations can respond predictably to ecological challenges. Convergence often results from similar genetic changes, which can emerge in two ways: the evolution of similar or identical mutations in independent lineages, which is termed parallel evolution; and the evolution in independent lineages of alleles that are shared among populations, which I call collateral genetic evolution. Evidence for parallel and collateral evolution has been found in many taxa, and an emerging hypothesis is that they result from the fact that mutations in some genetic targets minimize pleiotropic effects while simultaneously maximizing adaptation. If this proves correct, then the molecular changes underlying adaptation might be more predictable than has been appreciated previously. © 2013 Macmillan Publishers Limited.


Chan D.C.,Howard Hughes Medical Institute
Annual Review of Genetics | Year: 2012

Mitochondria are dynamic organelles that continually undergo fusion and fission. These opposing processes work in concert to maintain the shape, size, and number of mitochondria and their physiological function. Some of the major molecules mediating mitochondrial fusion and fission in mammals have been discovered, but the underlying molecular mechanisms are only partially unraveled. In particular, the cast of characters involved in mitochondrial fission needs to be clarified. By enabling content mixing between mitochondria, fusion and fission serve to maintain a homogeneous and healthy mitochondrial population. Mitochondrial dynamics has been linked to multiple mitochondrial functions, including mitochondrial DNA stability, respiratory capacity, apoptosis, response to cellular stress, and mitophagy. Because of these important functions, mitochondrial fusion and fission are essential in mammals, and even mild defects in mitochondrial dynamics are associated with disease. A better understanding of these processes likely will ultimately lead to improvements in human health. © 2012 by Annual Reviews.

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