The first step in gene expression is the formation of an RNA copy of its DNA. This step, called transcription, takes place in the cell nucleus. Transcription requires an enzyme called RNA polymerase to catalyze the synthesis of the RNA from the DNA template. This, in addition to other processing factors, is needed before messenger RNA (mRNA) can be exported to the cytoplasm, the area surrounding the nucleus.

Although the biochemical details of transcription and RNA processing are known, relatively little is understood about their cellular organization. Joseph G. Gall has been an intellectual leader and has made seminal breakthroughs in our understanding of chromosomes, nuclei and cells for nearly 60 years.   He is particularly  interested in how the structure of the nucleus is related to the synthesis and processing of RNA—specifically, what changes occur in the chromosomes and other nuclear components when RNA is synthesized, processed, and transported to the cytoplasm.

The researchers concentrate on a structure in the nucleus called the Cajal body, so named because it was first described 100 years ago by the Spanish neurobiologist and Nobel laureate Ramon y Cajal. Until recently very little was known about the Cajal body, but modern microscopical techniques  have brought rapid progress. Cajal bodies are now known to contain many factors involved in transcribing and modifying both pre-messenger RNA and pre-ribosomal RNA. Gall thinks that the Cajal body is a site for assembly of factors required for transcription and RNA processing.

Much of the lab’s work is carried out with unlaid eggs removed from the female frog Xenopus. These eggs, called oocytes, are giant cells up to 1.5 millimeters (mm) in diameter with a nucleus, or germinal vesicle (GV), 0.4 mm in diameter. The large GV permits scientists to examine the contents and structure of the nucleus in unprecedented detail.

The lab also used the fruit fly Drosophila cells , which are much smaller than frog cells, but have the advantage that they permit genetic studies on Cajal body components. In Drosophila one can manipulate the genes that encode proteins and RNAs of the Cajal body, and follow the consequences in various embryonic, larval, and adult tissues.

Gall has received numerous awards in acknowledgment of his special contributions, including the Albert Lasker Special Achievement Award in Medical Research, and the Lifetime Achievement Award of the Society for Developmental Biology, among others.

From 1952 to 1964 Gall taught zoology at the University of Minnesota. From 1964 to1983 he was the Ross Granville Harrison Professor of Biology, Professor of Molecular Biophysics and Biochemistry, at Yale University. In1983 he joined the Carnegie Institution as a staff scientist. For more see the Gall lab

Explore Carnegie Science

Experimental zebrafish larvae, courtesy Navid Marvi.
August 7, 2020

Baltimore, MD—New work led by Carnegie’s Meredith Wilson and Steve Farber identifies a potential therapeutic target for clogged arteries and other health risks that stem from an excess of harmful fats in the bloodstream.  Their findings are published by PLOS Genetics. 

“Cardiovascular disease occurs when lipids from the blood plasma are deposited in the walls of blood vessels, ultimately restricting blood flow,” explained Farber, who specializes in elucidating how cells process lipids. “This complex disease affects about a third of the world’s population, so improving our understanding of the mechanisms that regulate the levels of

Xenia in Carnegie's coral facility, courtesy Carnegie Embryology
June 17, 2020

Baltimore, MD— New work from a team of Carnegie cell, genomic, and developmental biologists solves a longstanding marine science mystery that could aid coral conservation. The researchers identified the type of cell that enables a soft coral to recognize and take up the photosynthetic algae with which it maintains a symbiotic relationship, as well as the genes responsible for this transaction.

Their breakthrough research is published in Nature.

Corals are marine invertebrates that build large exoskeletons from which reefs are constructed. But this architecture is only possible because of a mutually beneficial relationship between the coral and various species of

Yixian Zheng
March 11, 2020

Baltimore, MD— Carnegie’s Director of Embryology Yixian Zheng is one of 15 scientists awarded a grant from the Gordon and Betty Moore Foundation to support research on symbiosis in aquatic systems.

For the past two years, Zheng and her colleagues have been working to elucidate the molecular mechanisms of endosymbiosis in the relationships between coral and jellyfish and the photosynthetic algal species that they host. She has been building on Carnegie’s longstanding tradition of model organism development to begin revealing the genetics underlying the uptake and sustenance of symbiotic dinoflagellates by the soft coral species Xenia.

“I have always

Illustration courtesy of Navid Marvi and Andres Aranda-Diaz.
March 5, 2020

Baltimore, MD—Antibiotics can make easy work of infections. But how do they affect the complex ecosystems of friendly bacteria that make up our microbiome?

“When a doctor prescribes antibiotics, it sets up a multi-faceted experiment in your gastrointestinal system,” explains Carnegie’s Will Ludington “What can it teach us about the molecular principles of species interactions in nature?”

New work led by Ludington and Stanford University’s K.C. Huang set out to answer this challenging question and discovered a new form of antibiotic tolerance. Their findings, which have important health implications, are published by eLife.

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The Zheng lab studies cell division including the study of stem cells, genome organization, and lineage specification. They study the mechanism of genome organization in development, homeostasis—metabolic balance-- and aging; and the influence of cell morphogenesis, or cell shape and steructure,  on cell fate decisions. They use a wide range of tools and systems, including genetics in model organisms, cell culture, biochemistry, proteomics, and genomics.

 

The Spradling laboratory studies the biology of reproduction. By unknown means eggs reset the normally irreversible processes of differentiation and aging. The fruit fly Drosophila provides a favorable multicellular system for molecular genetic studies. The lab focuses on several aspects of egg development, called oogenesis, which promises to provide insight into the rejuvenation of the nucleus and surrounding cytoplasm. By studying ovarian stem cells, they are learning how cells maintain an undifferentiated state and how cell production is regulated by microenvironments known as niches. They are  also re-investigating the role of steroid and prostaglandin hormones in controlling

The Marnie Halpern laboratory studies how left-right differences arise in the developing brain and discovers the genes that control this asymmetry. Using the tiny zebrafish, Danio rerio, they explores how regional specializations occur within the neural tube, the embryonic tissue that develops into the brain and spinal cord.

The zebrafish is ideal for these studies because its basic body plan is set within 24 hours of fertilization. By day five, young larvae are able to feed and swim, and within three months they are ready to reproduce. They are also prolific breeders. Most importantly the embryos are transparent, allowing scientists to watch the nervous system develop and to

The Gall laboratory studies all aspects of the cell nucleus, particularly the structure of chromosomes, the transcription and processing of RNA, and the role of bodies inside the cell nucleus, especially the Cajal body (CB) and the histone locus body (HLB).

Much of the work makes use of the giant oocyte of amphibians and the equally giant nucleus or germinal vesicle (GV) found in it. He is particularly  interested in how the structure of the nucleus is related to the synthesis and processing of RNA—specifically, what changes occur in the chromosomes and other nuclear components when RNA is synthesized, processed, and transported to the cytoplasm.

Brittany Belin joined the Department of Embryology staff in August 2020. Her Ph.D. research involved developing new tools for in vivo imaging of actin in cell nuclei. Actin is a major structural element in eukaryotic cells—cells with a nucleus and organelles —forming contractile polymers that drive muscle contraction, the migration of immune cells to  infection sites, and the movement of signals from one part of a cell to another. Using the tools developed in her Ph.D., Belin discovered a new role for actin in aiding the repair of DNA breaks in human cells caused by carcinogens, UV light, and other mutagens.

Belin changed course for her postdoctoral work, in

Evolutionary geneticist Moises Exposito-Alonso joined the Department of Plant Biology as a staff associate in September 2019. He investigates whether and how plants will evolve to keep pace with climate change by conducting large-scale ecological and genome sequencing experiments. He also develops computational methods to derive fundamental principles of evolution, such as how fast natural populations acquire new mutations and how past climates shaped continental-scale biodiversity patterns. His goal is to use these first principles and computational approaches to forecast evolutionary outcomes of populations under climate change to anticipate potential future

Staff Associate Kamena Kostova joined the Department of Embryology in November 2018. She studies ribosomes, the factory-like structures inside cells that produce proteins. Scientists have known about ribosome structure, function, and biogenesis for some time. But, a major unanswered question is how cells monitor the integrity of the ribosome itself. Problems with ribosomes have been associated with diseases including neurodegeneration and cancer. The Kostova lab investigates the fundamental question of how cells respond when their ribosomes break down using mass spectrometry, functional genomics methods, and CRISPR genome editing.

Kostova received a B.S. in Biology from the

Sally June Tracy applies cutting-edge experimental and analytical techniques to understand the fundamental physical behavior of materials at extreme conditions. She uses dynamic compression techniques with high-flux X-ray sources to probe the structural changes and phase transitions in materials at conditions that mimic impacts and the interiors of terrestrial and exoplanets. She is also an expert in nuclear resonant scattering and synchrotron X-ray diffraction. She uses these techniques to understand novel behavior at the electronic level.  Tracy received her Ph.D. from the California Institute of