Growing up in Brazil, Marcos Simões-Costa typically visited his grandparents’ farm within the Amazon. That immersion in nature — squawking toucans and all — sparked his fascination with science and evolution. But a video of a growing embryo, proven in his center faculty science class, cemented his need to turn into a developmental biologist.
“It’s such a beautiful process,” he says. “I was always into drawing and art, and it was very visual — the shapes of the embryo changing, the fact that you start with one cell and the complexity is increasing. I just got lost in that video.”
Today, Simões-Costa, of Harvard Medical School and Boston Children’s Hospital, is honoring his youthful self by demystifying how the embryo develops. He research the embryos and stem cells of birds and mice to learn the way networks of genes and the weather that management them affect the identification of cells. The work may result in new remedies for numerous ailments, together with most cancers.
“The embryo is our best teacher,” he says.
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Standout analysis
Simões-Costa focuses on the embryo’s neural crest cells, a inhabitants of stem cells that type within the growing central nervous system. The cells migrate to different components of the embryo and provides rise to many various cell sorts, from the bone cells of the face to muscle cells to mind and nerve cells.
Scientists have questioned for years why, regardless of being so related, neural crest cells within the cranial area of the embryo can type bone and cartilage, whereas these within the trunk area can’t type both. While a postdoc at Caltech, Simões-Costa studied the cascade of molecules that govern how genes are expressed in every cell sort. With his adviser, developmental biologist Marianne Bronner, he recognized transcription components — proteins that may flip genes on and off — that have been current solely in cranial cells. Transplanting the genes for these proteins into trunk cells endowed the cells with the flexibility to create cartilage and bone.
Now in his personal lab, he continues to piece collectively simply how this huge regulatory community influences the specialization of cells. His staff reconstructed how neural crest cells’ full set of genetic directions, or the genome, folds right into a compact, 3-D form. The researchers recognized brief DNA sequences, referred to as enhancers, which are positioned in faraway areas of the genome, however find yourself near key genes when the genome folds. These enhancers work with transcription components and different regulatory components to regulate gene exercise.
Simões-Costa can be utilizing neural crest cells to elucidate an odd conduct shared by most cancers cells and a few embryonic cells. These cells produce power anaerobically, with out oxygen, even when oxygen is current. Called the Warburg impact, this metabolic course of has been studied extensively in most cancers cells, however its operate remained unclear.
Through experiments manipulating the metabolism of neural crest cells, Simões-Costa’s staff discovered that the Warburg impact is important for the cells to maneuver round throughout early improvement. The mechanism, which ought to keep turned off in nonembryonic cells, someway “gets reactivated in adult cells in the context of cancer, leading those cells to become more migratory and more invasive,” Simões-Costa says.
“He’s one of the few people who’s really looked at [this process in neural crest cells] at a molecular level and done a deep dive into the mechanisms underlying it,” says Bronner.
Cleverly combining classical embryological strategies with the newest genomic applied sciences to deal with elementary questions in developmental biology is what makes Simões-Costa particular, says Kelly Liu, a developmental biologist at Cornell University. He needs to grasp not solely what particular person genes do, however how they work at a methods stage, she says.
What’s subsequent
How does the genetic blueprint inform cells the place they’re within the embryo, and what they need to be doing? How do most cancers cells hijack the Warburg impact, and will understanding of that course of result in new remedies? These are a number of the questions Simões-Costa needs to deal with subsequent.
“It’s been 20 years since the Human Genome Project came to a conclusion,” he says, referring to the large effort to learn the human genetic instruction guide. “But there’s still so much mystery in the genetic code.”
Those mysteries, plus a deep ardour for lab work, gasoline Simões-Costa’s analysis. “Being at the bench is when I’m the happiest,” he says. He likens the fragile craft of performing exact surgical procedures on tissues and cells to meditation. “It does not get old.”
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