Integrity of hereditary material—the genome —is critical for species survival. Genomes need protection from agents that can cause mutations affecting DNA coding, regulatory functions, and duplication during cell division. DNA sequences called transposons, or jumping genes (discovered by Carnegie’s Barbara McClintock,) can multiply and randomly jump around the genome and cause mutations. About half of the sequence of the human and mouse genomes is derived from these mobile elements.  RNA interference (RNAi, codiscovered by Carnegie’s Andy Fire) and related processes are central to transposon control, particularly in egg and sperm precursor cells.  

The Bortvin lab, with colleagues, identified a key protein that suppresses jumping genes in mouse sperm and found that the protein is vital to sperm formation. It had been known previously that a similar element did this in the fruit fly. The protein, called Maelstrom, is old evolutionarily and found in many organisms. It is implicated in transposon silencing in flies and mice by means of specialized small RNAs known as Piwi-interacting RNAs (or piRNAs).  

Bortvin’s group showed the critical role of transposon silencing for normal fertility of male mice. But only recently did they discover the impact of transposons on the mammalian egg precursor.  The group found that mouse oocytes repress transposons inefficiently. Because of this poor transposon silencing, every oocyte stores this potent mutagen. Safia Malki in the lab correlated transposon abundance with oocyte viability and oocyte cell division reliability. She found that a burst of activity of a single transposon in transgenic mice increased oocyte death. Most strikingly, Malki improved oocyte viability and prevented errors in chromosome segregation by blocking the ability of the transposon to copy itself using a drug that blocks multiplication of HIV, the AIDS-causing virus.

 

This unique mode of transposon control in mouse oocytes sheds light on two puzzles—prenatal death of most oocytes and the age-related increase in chromosome errors, such as those that cause Down syndrome. Malki and Bortvin speculate that the lax control of transposons in mice, and perhaps human oocytes, causes the elimination of oocytes with either highly active transposons or those incapable of more stringent transposon control.

The surviving oocytes may prevent excessive transposon alterations to the genomes and be better suited to support the healthy development of the next generation. The Malki and Bortvin findings also suggest that an ovary of a newborn girl already contains “good” oocytes as well as those predisposed for chromosomal errors. It may be the case that “good” oocytes are ovulated during first two decades of a female’s reproductive life, while “bad” ones are ovulated later.

Bortvin received his Ph. D. in genetics from Harvard and was a postdoctoral fellow at the Whitehead Institute before joining the Carnegie staff in 2004. For more information see Bortvin lab

 

Explore Carnegie Science

November 10, 2016

Baltimore, MD—A first-of-its-kind study on almost 20,000 K-12 underrepresented public school students shows that Project BioEYES, based at Carnegie’s Department of Embryology, is effective at increasing students’ science knowledge and positive attitudes about science. Younger students had the greatest attitude changes. The study covered five years and tested students before and after the one-week BioEYES program. The research is published in the November 10, 2016, issue of PLOS Biology.

BioEYES (www.bioeyes.org) uses live zebrafish to teach basic scientific principles, animal development, and genetics. The zebrafish embryo is clear, making it ideal for observations. Each BioEYES

Carnegie Science, Carnegie Institution, Carnegie Institution for Science
November 2, 2016

Baltimore, MD— New work led by Carnegie’s Steven Farber, with help from Yixian Zheng’s lab, sheds light on how form follows function for intestinal cells responding to high-fat foods that are rich in cholesterol and triglycerides. Their findings are published in the Journal of Biological Chemistry.

Enterocytes are specialized cells that line the insides of our intestines. The intestinal surface is like a toothbrush, with lots of grooves and protrusions that allow the cells there to grab and absorb nutrients from food as it is digested, including the lipid molecules from fatty foods. The cells absorb, process, and package these lipids for distribution throughout our bodies. Clearly

Carnegie Science, Carnegie Institution, Carnegie Institution for Science
October 5, 2016

Baltimore, MD---Athletes, the elderly and those with degenerative muscle disease would all benefit from accelerated muscle repair. When skeletal muscles, those connected to the bone, are injured, muscle stem cells wake up from a dormant state and repair the damage. When muscles age, however, stem cell number and function declines, as do both tissue function and regenerative ability.  Carnegie’s Christoph Lepper and team*, including researchers from the University of Missouri, investigated muscle stem cell pool size. In particular, they asked if stem cell number could be increased, and if there would be any associated functional benefits.

Using genetically modified mice, the

September 23, 2016

Washington, D.C.—  Zehra Nizami has been a graduate student and postdoc in Joe Gall’s lab at the Department of Embryology. She is the fourth recipient of the Postdoctoral Innovation and Excellence (PIE) Award, which are made through nominations from the department directors and chosen by the Office of the President. Her career at Embryology includes outstanding accomplishments in the three areas recognized by the PIE Award—science, education, and community service.

Nizami is co-discoverer of a new class of RNA molecules in amphibian egg cells called stable intronic sequence (sis) RNA. These sequences were not anticipated. It was believed for 35 years that introns—bits of DNA that

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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

Stem cells make headline news as potential treatments for a variety of diseases. But undertstanding the nuts and bolts of how they develop from an undifferentiated cell  that gives rise to cells that are specialized such as organs, or bones, and the nervous system, is not well understood. 

The Lepper lab studies the mechanics of these processes. overturned previous research that identified critical genes for making muscle stem cells. It turns out that the genes that make muscle stem cells in the embryo are surprisingly not needed in adult muscle stem cells to regenerate muscles after injury. The finding challenges the current course of research into muscular dystrophy, muscle

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

Peter van Keken studies the thermal and chemical evolution of the Earth. In particularly he looks at the causes and consequences of plate tectonics; element modeling of mantle convection,  and the dynamics of subduction zones--locations where one tectonic plate slides under another. He also studies mantle plumes; the integration of geodynamics with seismology; geochemistry and mineral physics. He uses parallel computing and scientific visualization in this work.

He received his BS and Ph D from the University of Utrecht in The Netherlands. Prior to joining Carnegie he was on the faculty of the University of Michigan.

Peter Driscoll studies the evolution of Earth’s core and magnetic field including magnetic pole reversal. Over the last 20 million or so years, the north and south magnetic poles on Earth have reversed about every 200,000, to 300,000 years and is now long overdue. He also investigates the Earth’s inner core structure; core-mantle coupling; tectonic-volatile cycling; orbital migration—how Earth’s orbit moves—and tidal dissipation—the dissipation of tidal forces between two closely orbiting bodies. He is also interested in planetary interiors, dynamos, upper planetary atmospheres and exoplanets—planets orbiting other stars. He uses large-scale numerical simulations in much of his research

Andrew Newman works in several areas in extragalactic astronomy, including the distribution of dark matter--the mysterious, invisible  matter that makes up most of the universe--on galaxies, the evolution of the structure and dynamics of massive early galaxies including dwarf galaxies, ellipticals and cluster. He uses tools such as gravitational lensing, stellar dynamics, and stellar population synthesis from data gathered from the Magellan, Keck, Palomar, and Hubble telescopes.

Newman received his AB in physics and mathematics from the Washington University in St. Louis, and his MS and Ph D in astrophysics from Caltech. Before becomming a staff astronomer in 2015, he was a

Gwen Rudie studies the chemical and physical properties of very distant, so-called  high-redshift galaxies and their surrounding circumgalactic medium. She is primarily an observational astronomer working on the analysis and interpretation of high-resolution spectroscopy of high-redshift Quasi Stellar Objects and low to medium-resolution near-infrared and optical spectroscopy of high-redshift galaxies. She is interested in understanding the intergalactic medium as a tool for understanding galaxy evolution and the physical properties of very distant galaxies such as the composition of stars and their star formation rates

Rudie received her AB from Dartmouth College and her Ph D