Khaled Khairy

Bio: Khaled Khairy is an academic researcher from Howard Hughes Medical Institute. The author has contributed to research in topics: Light sheet fluorescence microscopy & Spherical harmonics. The author has an hindex of 19, co-authored 34 publications receiving 2646 citations. Previous affiliations of Khaled Khairy include St. Jude Children's Research Hospital & Max Planck Society.

A connectome and analysis of the adult Drosophila central brain

Abstract: Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons – compared to some 86 billion in humans – the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map – or connectome – the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path.

Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy

Abstract: The combination of digital scanned laser light sheet microscopy and incoherent structured illumination allows intrinsic removal of scattered background fluorescence from the desired fluorescent signal. This provides substantial advantages for imaging nontransparent organisms and allowed reconstruction of a fly digital embryo from a developing Drosophila embryo.

Quantitative high-speed imaging of entire developing embryos with simultaneous multiview light-sheet microscopy.

Abstract: Simultaneous multiview light-sheet microscopy using two illumination and two detection arms with one- or two-photon illumination is coupled to a fast data acquisition framework and analysis pipeline for quantitative imaging and tracking of individual cells and the developing nervous system throughout a living fly embryo. A related paper by Krzic et al. is also in this issue.

A Complete Electron Microscopy Volume Of The Brain Of Adult Drosophila melanogaster

Abstract: Drosophila melanogaster has a rich repertoire of innate and learned behaviors Its 100,000-neuron brain is a large but tractable target for comprehensive neural circuit mapping Only electron microscopy (EM) enables complete, unbiased mapping of synaptic connectivity; however, the fly brain is too large for conventional EM We developed a custom high-throughput EM platform and imaged the entire brain of an adult female fly We validated the dataset by tracing brain-spanning circuitry involving the mushroom body (MB), intensively studied for its role in learning Here we describe the complete set of olfactory inputs to the MB; find a new cell type providing driving input to Kenyon cells (the intrinsic MB neurons); identify neurons postsynaptic to Kenyon cell dendrites; and find that axonal arbors providing input to the MB calyx are more tightly clustered than previously indicated by light-level data This freely available EM dataset will significantly accelerate Drosophila neuroscience

Pattern Recognition and Machine Learning

Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

Abstract: Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Lattice Light Sheet Microscopy: Imaging Molecules to Embryos at High Spatiotemporal Resolution

Abstract: Although fluorescence microscopy provides a crucial window into the physiology of living specimens, many biological processes are too fragile, are too small, or occur too rapidly to see clearly with existing tools. We crafted ultrathin light sheets from two-dimensional optical lattices that allowed us to image three-dimensional (3D) dynamics for hundreds of volumes, often at subsecond intervals, at the diffraction limit and beyond. We applied this to systems spanning four orders of magnitude in space and time, including the diffusion of single transcription factor molecules in stem cell spheroids, the dynamic instability of mitotic microtubules, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in Caenorhabditis elegans and Drosophila melanogaster. The results provide a visceral reminder of the beauty and the complexity of living systems.

Advanced methods of microscope control using μManager software.

Abstract: μManager is an open-source, cross-platform desktop application, to control a wide variety of motorized microscopes, scientific cameras, stages, illuminators, and other microscope accessories. Since its inception in 2005, μManager has grown to support a wide range of microscopy hardware and is now used by thousands of researchers around the world. The application provides a mature graphical user interface and offers open programming interfaces to facilitate plugins and scripts. Here, we present a guide to using some of the recently added advanced μManager features, including hardware synchronization, simultaneous use of multiple cameras, projection of patterned light onto a specimen, live slide mapping, imaging with multi-well plates, particle localization and tracking, and high-speed imaging.