Marcos Simões-Costa asks how cells within the embryo get their identities


Rising up in Brazil, Marcos Simões-Costa usually visited his grandparents’ farm within the Amazon. That immersion in nature — squawking toucans and all — sparked his fascination with science and evolution. However a video of a growing embryo, proven in his center faculty science class, cemented his want to develop into a developmental biologist.

“It’s such a ravishing course of,” he says. “I used to be at all times into drawing and artwork, and it was very visible — the shapes of the embryo altering, the truth that you begin with one cell and the complexity is rising. I simply bought misplaced in that video.”

At the moment, Simões-Costa, of Harvard Medical Faculty and Boston Kids’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 find out how networks of genes and the weather that management them affect the identification of cells. The work might result in new remedies for varied illnesses, together with most cancers.

“The embryo is our greatest instructor,” 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 elements 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 puzzled for years why, regardless of being so comparable, 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. Whereas a postdoc at Caltech, Simões-Costa studied the cascade of molecules that govern how genes are expressed in every cell kind. Along 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 workforce 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, known as enhancers, which might be 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 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. Known as the Warburg impact, this metabolic course of has been studied extensively in most cancers cells, however its operate remained unclear.

When neural crest cells are soaked with a drug that forces them to metabolize oxygen, they don’t transfer as a lot (proper) as cells that aren’t handled (left). Cell actions are tracked over 12 hours. D. Bhattacharya, A.P. Azambuja, M. Simões-Costa/Developmental Cell 2020

When neural crest cells are soaked with a drug that forces them to metabolize oxygen, they don’t transfer as a lot (backside) as cells that aren’t handled (prime). Cell actions are tracked over 12 hours. D. Bhattacharya, A.P. Azambuja, M. Simões-Costa/Developmental Cell 2020

Via experiments manipulating the metabolism of neural crest cells, Simões-Costa’s workforce discovered that the Warburg impact is critical for the cells to maneuver round throughout early improvement. The mechanism, which ought to keep turned off in nonembryonic cells, someway “will get reactivated in grownup cells within the context of most cancers, main these cells to develop into extra migratory and extra invasive,” Simões-Costa says.

“He’s one of many few individuals who’s actually checked out [this process in neural crest cells] at a molecular stage and achieved 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 College. He needs to know not solely what particular person genes do, however how they work at a programs 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 sort out subsequent.

“It’s been 20 years for the reason that Human Genome Challenge got here to a conclusion,” he says, referring to the large effort to learn the human genetic instruction guide. “However there’s nonetheless a lot thriller within the genetic code.”

These mysteries, plus a deep ardour for lab work, gas Simões-Costa’s analysis. “Being on the bench is after I’m the happiest,” he says. He likens the fragile craft of performing exact surgical procedures on tissues and cells to meditation. “It doesn’t get previous.”

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