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

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Kamena Kostova, courtesy Navid Marvi, Carnegie Institution for Science
October 1, 2019

Baltimore, MD— Carnegie biologist Kamena Kostova has been selected for the Director’s Early Independence Award from the National Institutes of Health, which is designed to provide “exceptional junior scientists” with the opportunity to “skip traditional post-doctoral training and move immediately into independent research positions.”

Kostova is one of 13 recipients of the 2019 Early Independence Award. The recognition is part of a suite of four that comprise the NIH Director’s High-Risk, High-Reward Research Program, which honors “highly innovative biomedical or behavioral research proposed by extraordinarily creative scientists.

GDNF repairs aged muscle stem cells courtesy of Liangji Li.
September 30, 2019

Washington, DC— An age-related decline in recovery from muscle injury can be traced to a protein that suppresses the special ability of muscle stem cells to build new muscles, according to work from a team of current and former Carnegie biologists led by Chen-Ming Fan and published in Nature Metabolism.

Skeletal muscles have a tremendous capacity to make new muscles from special muscle stem cells. These “blank” cells are not only good at making muscles but also at generating more of themselves, a process called self-renewal. But their amazing abilities diminish with age, resulting in poorer muscle regeneration from muscle trauma.

The research team—

This image captures the bright blue light (chemiluminesc ence) emitted by the NanoLuc protein in LipoGlo zebrafish. It is is provided courtesy of James Thierer.
July 31, 2019

Baltimore, MD—A newly developed technique that shows artery clogging fat-and-protein complexes in live fish gave investigators from Carnegie, Johns Hopkins University, and the Mayo Clinic a glimpse of how to study heart disease in action. Their research, which is currently being used to find new drugs to fight cardiovascular disease, is now published in Nature Communications.

Fat molecules, also called lipids, such as cholesterol and triglycerides are shuttled around the circulatory system by a protein called Apolipoprotein-B, or ApoB for short. These complexes of lipid and protein are called lipoproteins but may be more commonly known as “bad cholesterol.”

One analogy for understanding the mathematical structure of the team's work is to think of it as foam being simplified into a single bubble by progressively merging adjacent bubbles.
July 2, 2019

Baltimore, MD—How do the communities of microbes living in our gastrointestinal systems affect our health? Carnegie’s Will Ludington was part of a team that helped answer this question.

For nearly a century, evolutionary biologists have probed how genes encode an individual’s chances for success—or fitness—in a specific environment.

In order to reveal a potential evolutionary trajectory biologists measure the interactions between genes to see which combinations are most fit.  An organism that is evolving should take the most fit path. This concept is called a fitness landscape, and various mathematical techniques have been developed to

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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.

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

The Ludington lab investigates complex ecological dynamics from microbial community interactions using the fruit fly  Drosophila melanogaster. The fruit fly gut carries numerous microbial species, which can be cultured in the lab. The goal is to understand the gut ecology and how it relates to host health, among other questions, by taking advantage of the fast time-scale and ease of studying the fruit fly in controlled experiments.