Growing up in Brazil, Marcos Simões-Costa typically visited his grandparents’ farm in the Amazon. That immersion in nature — squawking toucans and all — sparked his fascination with science and evolution. But a video of a creating embryo, proven in his center college science class, cemented his need to grow to be 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 study how networks of genes and the components that management them affect the id of cells. The work might result in new remedies for numerous illnesses, together with most cancers.
“The embryo is our best teacher,” he says.
Simões-Costa focuses on the embryo’s neural crest cells, a inhabitants of stem cells that kind in the creating central nervous system. The cells migrate to different elements of the embryo and provides rise to many alternative cell varieties, from the bone cells of the face to muscle cells to mind and nerve cells.
Scientists have puzzled for years why, regardless of being so comparable, neural crest cells in the cranial area of the embryo can kind bone and cartilage, whereas these in the trunk area can’t kind 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 elements — proteins that may flip genes on and off — that had been current solely in cranial cells. Transplanting the genes for these proteins into trunk cells endowed the cells with the capability 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 crew 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 situated in faraway areas of the genome, however find yourself near key genes when the genome folds. These enhancers work with transcription elements and different regulatory components to regulate gene exercise.
Simões-Costa can also be utilizing neural crest cells to elucidate a wierd 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 perform remained unclear.
Through experiments manipulating the metabolism of neural crest cells, Simões-Costa’s crew discovered that the Warburg impact is important for the cells to maneuver round throughout early growth. The mechanism, which ought to keep turned off in nonembryonic cells, in some way “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 basic questions in developmental biology is what makes Simões-Costa particular, says Kelly Liu, a developmental biologist at Cornell University. He desires to know not solely what particular person genes do, however how they work at a programs degree, she says.
How does the genetic blueprint inform cells the place they’re in 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 few of the questions Simões-Costa desires to sort out subsequent.
“It’s been 20 years since the Human Genome Project came to a conclusion,” he says, referring to the huge effort to read the human genetic instruction book. “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 delicate craft of performing exact surgical procedures on tissues and cells to meditation. “It does not get old.”
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