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

October 10, 2018

Carnegie’s Department of Embryology scientist Steven Farber and team have been awarded a 5-year $3.3-million NIH grant to identify novel pharmaceuticals for combating a host of diseases associated with altered levels of lipoproteins like LDL (“bad cholesterol”). Obesity, diabetes, cardiovascular disease, fatty liver disease, and metabolic syndrome have all been linked to changes in plasma lipoproteins. 

Lab efforts, led by graduate student Jay Thierer, started by creating zebrafish that have been genetically engineered to produce glowing lipoproteins, a technique they call “LipoGlo”. This was achieved by attaching DNA encoding NanoLuc (a relative of the protein that makes

October 1, 2018

Tasuku Honjo, a postdoctoral fellow in the Brown Lab at the Department of Embryology 1971-1973, shares the 2018 Nobel Prize in Physiology or Medicine.

The AsianScientist quoted Honjo as saying: "After I moved to the US as a postdoctoral researcher in the 70s, I met my mentor, Dr. Donald Brown, at the Carnegie Institution for Science in Baltimore. He told me that the major question of immunology at the time was, how do we create such an enormous diversity of antibodies? That question is now ready to be tackled using a molecular strategy." Read the official Nobel press release. Image courtesy Nobel.org

 

 

 

September 20, 2018

Baltimore, MD— Body organs such as the intestine and ovaries undergo structural changes in response to dietary nutrients that can have lasting impacts on metabolism, as well as cancer susceptibility, according to Carnegie’s Rebecca Obniski, Matthew Sieber, and Allan Spradling.

Their work, published by Developmental Cell, used fruit flies, which are currently the most-sensitive experimental system for such detecting diet-induced cellular changes that are likely to be similar in mammals.

There are three major types of cells in fruit fly (and mammalian) intestines: Stem cells, hormone-producing cells, and nutrient-handling cells. Think of the stem cells as blanks, which are

September 18, 2018

Ethan Greenblatt, a senior postdoctoral associate in Allan Spradling’s lab at the Department of Embryology, has been awarded the eleventh Postdoctoral Innovation and Excellence Award. Greenblatt has made a major impact on biological science, particularly with his research identifying genetic factors underlying fragile X syndrome, the most common cause of autism.

Recipients of these postdoctoral awards are given a cash prize for their exceptionally creative approaches to science, strong mentoring, and contributing to the sense of campus community. A celebration is also held in their honor. These awards are made through nominations from the departments and are chosen by the Office

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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

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. 

Nick Konidaris is a staff scientist at the Carnegie Observatories and Instrument Lead for the SDSS-V Local Volume Mapper (LVM). He works on a broad range of new optical instrumentation projects in astronomy and remote sensing. Nick's projects range from experimental to large workhorse facilities. On the experimental side, he recently began working on a new development platform for the 40-inch Swope telescope at Carnegie's Las Campanas Observatory that will be used to explore and understand the explosive universe.

 Nick and his colleagues at the Department of Global Ecology are leveraging the work on Swope to develop a new airborne spectrograph that will be used to provide a direct

Experimental petrologist Michael Walter became director of the Geophysical Laboratory beginning April 1, 2018. His recent research has focused on the period early in Earth’s history, shortly after the planet accreted from the cloud of gas and dust surrounding our young Sun, when the mantle and the core first separated into distinct layers. Current topics of investigation also include the structure and properties of various compounds under the extreme pressures and temperatures found deep inside the planet, and information about the pressure, temperature, and chemical conditions of the mantle that can be gleaned from mineral impurities preserved inside diamonds.

Walter had been at

Guoyin Shen's research interests lie in the quest to establish and to examine models for explaining and controlling the behavior of materials under extreme conditions. His research activities include investigation of phase transformations and melting lines in molecular solids, oxides and metals; polyamorphism in liquids and amorphous materials; new states of matter and their emergent properties under extreme conditions; and the development of enabling high-pressure synchrotron techniques for advancing compression science. 

He obtained a Ph.D. in mineral physics from Uppsala University, Sweden in 1994 and a B.S. in geochemistry from Zhejiang University, China in 1982. For more