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

Artist's conception of this research project courtesy of Navid Marvi
July 14, 2021

Baltimore, MD—Carnegie’s Steven Farber was awarded nearly $500,000 over three years by The G. Harold & Leila Y. Mathers Foundation to identify the chemical components of cinnamon oil that show effectiveness against cardiovascular disease-causing fats.

Fat molecules, or lipids, such as cholesterol and triglycerides are shuttled around the circulatory system by a protein called Apolipoprotein-B, together forming complexes of lipid and protein that are called lipoproteins but may be more commonly known as “bad cholesterol.” It can get embedded in the sides of blood vessels and harden, forming a dangerous buildup that makes it more difficult for the heart

Carnegie's William Ludington
July 14, 2021

Baltimore, MD—Carnegie William Ludington’s quest to understand the community ecology of our gut microbiome was this spring awarded nearly $1 million over three years from the National Science Foundation. He was also selected as one of 14 researchers to receive $55,000 from the Research Corporation for Science Advancement for its inaugural Scialog: Microbiome, Neurobiology, and Disease initiative.

“Since he arrived at Carnegie in 2018, Will has been aggressively pursuing breakthroughs in microbiome research—deploying a multitude of genetic, physiological, and mathematical approaches,” said Carnegie Embryology Director Yixian Zheng. “These two

Heart Reef in Australia's Great Barrier Reef, public domain.
December 21, 2020

Baltimore, MD— The CRISPR/Cas9 genome editing system can help scientists understand, and possibly improve, how corals respond to the environmental stresses of climate change. Work led by Phillip Cleves—who joined Carnegie’s Department of Embryology this fall—details how the revolutionary, Nobel Prize-winning technology can be deployed to guide conservation efforts for fragile reef ecosystems.

Cleves’ research team’s findings were recently published in two papers in the Proceedings of the National Academy of Sciences.

Corals are marine invertebrates that build extensive calcium carbonate skeletons from which reefs are constructed. But this

Orange peyssonnelid algal crusts courtesy of Peter Edmunds.
November 30, 2020

Baltimore, MD—Human activity endangers coral health around the world. A new algal threat is taking advantage of coral’s already precarious situation in the Caribbean and making it even harder for reef ecosystems to grow.

Just-published research in Scientific Reports details how an aggressive, golden-brown, crust-like alga is rapidly overgrowing shallow reefs, taking the place of coral that was damaged by extreme storms and exacerbating the damage caused by ocean acidification, disease, pollution, and bleaching.

For the past four years, the University of Oxford’s Bryan Wilson, Carnegie’s Chen‑Ming Fan, and California State University Northridge’

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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 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.

In mammals, most lipids, such as fatty acids and cholesterol, are absorbed into the body via the small intestine. The complexity of the cells and fluids that inhabit this organ make it very difficult to study in a laboratory setting. The goal of the Farber lab is to better understand the cell and molecular biology of lipids within digestive organs by exploiting the many unique attributes of the clear zebrafish larva  to visualize lipid uptake and processing in real time.  Given their utmost necessity for proper cellular function, it is not surprising that defects in lipid metabolism underlie a number of human diseases, including obesity, diabetes, and atherosclerosis.

Johanna Teske became the first new staff member to join Carnegie’s newly named Earth and Planets Laboratory (EPL) in Washington, D.C., on September 1, 2020. She has been a NASA Hubble Fellow at the Carnegie Observatories in Pasadena, CA, since 2018. From 2014 to 2017 she was the Carnegie Origins Postdoctoral Fellow—a joint position between Carnegie’s Department of Terrestrial Magnetism (now part of EPL) and the Carnegie Observatories.

Teske is interested in the diversity in exoplanet compositions and the origins of that diversity. She uses observations to estimate exoplanet interior and atmospheric compositions, and the chemical environments of their formation

Phillip Cleves’ Ph.D. research was on determining the genetic changes that drive morphological evolution. He used the emerging model organism, the stickleback fish, to map genetic changes that control skeletal evolution. Using new genetic mapping and reverse genetic tools developed during his Ph.D., Cleves identified regulatory changes in a protein called bone morphogenetic protein 6 that were responsible for an evolved increase in tooth number in stickleback. This work illustrated how molecular changes can generate morphological novelty in vertebrates.

Cleves returned to his passion for coral research in his postdoctoral work in John Pringles’ lab at Stanford

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