The mouse is a traditional model organism for understanding physiological processes in humans. Chen-Ming Fan uses the mouse to study the underlying mechanisms involved in human development and genetic diseases. He concentrates on identifying and understanding the signals that direct the musculoskeletal system to develop in the mammalian embryo. Skin, muscle, cartilage, and bone are all derived from a group of progenitor structures called somites. Various growth factors—molecules that stimulate the growth of cells—in the surrounding tissues work in concert to signal each somitic cell to differentiate into a specific tissue type.

The lab has identified various growth factors that have profound effects on somite development. The goal of the lab is to identify more factors, the pathways in which they operate, and the genes that control the processes.

They identified that the Hedgehog (Hh) proteins are responsible for inducing the early skeletal fate and an unexpected mechanism that provides a new vision of the signaling pathway of Hh. They also found that  the Wnt family of proteins plays a key role in inducing the skin/muscle dual potential progenitors and they  have uncovered previously unknown effectors and target genes of Wnt.

Somites not only supply cells for embryonic muscles, they also contain muscle progenitors.  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 injury, and regenerative medicine, which uses stem cells for healing tissues, and it favors using age-matched stem cells for therapy.

Researchers in the lab also study hormones involved with the hypothalamus, the essential brain center that maintains a balance of metabolic processes by modulating pituitary hormone secretions.  Studies of these hormones have been instrumental to our understanding of endocrine homeostasis, including the maintenance of proper concentrations of bodily fluid and the balance of energy metabolism.

Several genes, called Sim1, Sim2, and Gas1 are involved in musculoskeletal development. Sim1 also controls the developing hypothalamus.  The researchers found to their surprise that Sim1-heterozygous mice—having a pair of genes that are dissimilar for a hereditary characteristic—become obese from an uncontrollable appetite.  Human patients that are heterozygous for the Sim1 gene also display very early onset obesity. Since the hypothalamus has been implicated in the control of satiety, the researchers probe how Sim1 fits into the known genetic pathway involved in the obese condition.

Fan received his Ph. D. from Harvard University. He was a postdoctoral fellow at UC-San Francisco before coming to Carnegie as a staff researcher in 1995. For more see the Fan lab

 

Explore Carnegie Science

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’

October 8, 2020

Baltimore, MD— Recently published work from Carnegie’s Allan Spradling and Wanbao Niu revealed in unprecedented detail the genetic instructions immature egg cells go through step by step as they mature into functionality. Their findings improve our understanding of how ovaries maintain a female’s fertility.

The general outline of how immature egg cells are assisted by specific ovarian helper cells starting even before a female is born is well understood. But Spradling and Niu mapped the gene activity of thousands of immature egg cells and helper cells to learn how the stage is set for fertility later in life.

Even before birth, "germ" cells

October 8, 2020

Baltimore, MD— Recent work led by Carnegie’s Kamena Kostova revealed a new quality control system in the protein production assembly line with possible implications for understanding neurogenerative disease.

The DNA that comprises the chromosomes housed in each cell’s nucleus encodes the recipes for how to make proteins, which are responsible for the majority of the physiological actions that sustain life. Individual recipes are transcribed using messenger RNA, which carries this piece of code to a piece of cellular machinery called the ribosome. The ribosome translates the message into amino acids—the building blocks of proteins.

But sometimes

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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.

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