Cool Jobs: Puzzling over proteins to study life and death | Science News for Students

Cool Jobs: Puzzling over proteins to study life and death

Three research groups are discovering how tiny machines power cells, people and other animals
Sep 28, 2017 — 7:14 am EST
Protein foods

Most people think of fibrous and muscle-rich foods when they hear the word protein. In fact, every cell of the body makes proteins, which will carry out all of its many functions. Scientists are focusing on proteins — in cells and foods and fossils — to better understand how the body functions.

MillefloreImages/iStockphoto

Mary Schweitzer and her research team were studying the fossil of an 80-million-year-old duck-billed dinosaur. Suddenly, they noticed something odd. When they examined the dinosaur’s leg bone, they found ancient fragments of a protein called collagen (KAHL-eh-jen). This common protein is found in the cartilage, bones, skin and muscles of many animals, including humans. Schweitzer's team didn’t expect to find any trace of a protein in something so old.

Schweitzer is a dinosaur expert at North Carolina State University in Raleigh. She and her team want to understand more about how dinosaurs lived and died. But they’re not focusing only on the shape and size of these fossils. Instead, they’re digging into bones to reveal what the human eye can’t see. This team is studying the chemistry within ancient dinosaur bones.

375_inline_Brachylophosaurus-femur.png
Researchers found collagen protein in the fossilized leg bone of this duck-billed dinosaur (Brachylophosaurus canadensis) in what is now Montana. The “1” tag refers to the site where they took the sample containing collagen.  
Mary Schweitzer/UNC

This discovery and others have taught them an important lesson. “Fossils are not rocks,” Schweitzer says. “They actually have pieces and parts of the once-living animals within them.” Some fossils can contain soft and stretchy tissue, blood vessels and cells, she has found. Some can even hold onto chemicals like proteins, which scientists thought were too fragile to survive for millions of years.

How can they last that long? This is just one of many questions being asked of proteins, tiny molecules that act like chemical machines in our cells.

DNA provides each cell with an instruction book on how to make these bitty widgets. The machines a cell builds then do all the work to help it survive. Proteins carry in crucial supplies and take out the trash. They send important messages. They even fight off invaders.

Studying proteins gives scientists a better idea of how cells are supposed to work and what happens when they malfunction.

Schweitzer is among researchers taking a closer look at proteins’ many roles. A children’s doctor in St. Louis, Mo., is part of another team studying how protein-rich peanut butter could work like medicine to help kids in Africa. And a scientist in Seattle, Wash., is using glowing jellyfish proteins to light up — and label — parts of living cells to see how they work. 

Block by block

Our cells make proteins by piecing together basic chemical building blocks known as amino acids. Those cells choose from a standard kit of only 20 different amino acids. But cells can string them together in countless ways. The result is a remarkably diverse catalog of proteins.

So far, researchers have found the basic instructions — or genes — for about 21,000 human proteins. Including possible variations, though, the total number of different types could be as high as 250,000 to one million. Some are only needed for a short time. Cells can then recycle their amino acid parts to build new proteins. Others, such as collagen proteins, provide tissues such as bone and muscle with solid supports that are built to last.

scientist, paleontologist
Elena Schroeter digs up another fossil of a duck-billed dinosaur’s leg bone in South Dakota.
Courtesy of Project Exploration

Collagen’s strength comes from its structure. The amino acids in collagen I form a complicated braid known as a triple helix. This sturdy frame can link up with its neighbors to make a scaffold. Researchers think these connected supports keep collagen I from falling apart.

Finding collagen in fossils was a surprise. Recognizing its staying power might now prove quite useful. Schweitzer and Elena Schroeter have begun using proteins as clues to figure out how dinosaurs lived, grew and evolved. Schroeter is a postdoctoral researcher in Schweitzer’s lab. (She has her doctoral degree but is continuing to study before starting her own lab.)

Until recently, to study the dinosaur family tree paleontologists mostly relied on the shapes of related animals’ bones. The idea, here, is that an animal’s skeleton will be most similar to that of its closest relatives, Schroeter explains. “As you get more distantly related, the skeleton is [increasingly] different,” she says.

But dinosaur fossils are rare. Researchers often don’t have complete dinosaur skeletons. Bone comparisons only work if researchers can match up the same bones from different animals. For instance, Schroeter explains, you can’t compare an arm bone from one dinosaur to a tailbone from a second.

Biologists often compare the DNA of living animals to find out how closely related they are. But DNA is fragile and hard to collect from fossils. That’s why proteins could help. Collagen, for example, is less fragile than DNA. That should make it easier to study. And because DNA provides the template for making collagen, the protein can still point out differences among animals’ instruction books.

“The collagen in my arm bone and the collagen in my leg bone is the same,” Schroeter says. Slight differences in the protein between species might reveal how closely related the two animals were — and how they evolved over time.

Protein power

To collect dinosaur protein, Schroeter grinds up a fossilized bone. Then she adds the powder to chemicals in a liquid. These chemicals help separate protein pieces from mineral bits. A machine called a mass spectrometer can help identify the protein bits. This machine acts like a sensitive scale. It measures the mass of every protein fragment in the mixture. A computer program then matches those fragments to ones from known proteins. Like trying to fit puzzle pieces together, it determines which pieces are present. It also predicts how they would match up to form the original protein.

Someday, the methods used to identify dinosaur proteins might even help in the hunt for life on Mars. In both cases, Schweitzer explains, researchers would likely look for very old and tiny pieces of some type of molecule. If found and properly identified, molecules (such as proteins) might offer signs of long-ago life.

Brachylophosaurus
Eighty million years ago, duck-billed dinosaurs like this one (Latin name: Brachylophosaurus) roamed in what is now the western United States. Remarkably, scientists have found bits of protein remaining within some of the dinosaurs’ ancient bones.
Debivort/Wikipedia (CC BY-SA 3.0)

So far, Schweitzer and Schroeter have pieced together more than 10 percent of the collagen I protein in the duck-billed dinosaurs. That’s enough to place this animal between crocodiles and birds on the family tree of animals. More complete proteins might point out new links to other dinosaurs as well.

To fill in the family tree, Schweitzer and Schroeter are looking for collagen and other proteins in more fossils from duck-billed dinosaurs, from Tyrannosaurus rex and from other species.

Beyond showing how dinosaurs are related to animals that live today, proteins might unlock other secrets of these extinct animals. Imagine if researchers could identify proteins and other contents in a dinosaur’s stomach. If so, Schweitzer says, we might discover how certain dinosaurs became giants — like the sauropods. These plant-eaters, known for their long necks and tails, had unusually small mouths. Yet they could eat enough to grow from an egg to adults weighing more than 80 tons. How could they reach nearly half a football field in length?

Maybe ancient plants were more nutritious. Maybe the dinosaurs could digest plants more efficiently. In fact, learning what helped sauropods grow so big might help researchers identify old proteins that could prove useful even today.

“Dinosaurs had a lot of stuff figured out that we mammals haven’t achieved nearly so well,” Schweitzer says. “Maybe molecules hold the key.”

Protein power

Protein isn’t just important for studying bones. It’s a vital component of our diet. It’s found in food such as eggs, meat and milk. When you eat protein, your body dissolves it into its amino-acid building blocks. Those blocks can then be recycled to build new proteins for muscles. (That’s why bodybuilders eat so much high-protein food.) During childhood, kids also need plenty of protein for the construction projects taking place throughout the body.

peanut butter
Protein-packed peanut butter is helping to save kids with severe acute malnutrition in some parts of Africa.
deborahmiller56/ Pixabay (CC0)

If children don’t get enough to eat — or enough protein overall — their health will suffer. To improve the health of kids in Africa, proteins in foods such as peanut butter can pack a real punch.

Mark Manary is a pediatrician at Washington University in St. Louis. He’s always been driven to try and make the world a better place. After medical school, he worked at a hospital in the southeast African country of Malawi. There, he confronted a big problem. “Kids were sick because they didn’t get enough to eat,” he recalls. They were suffering from a life-threatening condition called severe acute malnutrition.  

And they were not alone. The United Nations International Children's Emergency Fund, or UNICEF, estimates that worldwide 16 million children under age 5 suffer from this condition. These kids are nine times as likely to die as are children who get enough healthy food.

“One of the most important capacities [our bodies] have is the ability to fight infection,” Manary explains. When malnourished, kids’ defenses begin to fall apart. “Your body needs these building blocks. It needs fresh vitamins and minerals and protein and everything to rebuild and restore itself every day,” he says. “And when it doesn’t get it, it starts wasting away.”

But it was difficult to provide malnourished kids with the right mix of protein-rich foods. In the hospital, Manary tried feeding them milk and other nutritious foods. But fewer than half of these got better.

Child, Africa
A young child in the African country of Malawi eats a paste made from peanut butter. Doctors call it an RUTF, or Ready-to-Use Therapeutic Food.
Photo courtesy of Mark Manary/Washington University

In fact, keeping kids in the hospital for a long time often made them worse. They often picked up diseases from other kids, notes Meghan Callaghan. She helps coordinate Manary’s research. In Malawi, parents sometimes took their kids home before they were well. At home, such families often struggled to provide the extra food their children needed.

The peanut butter solution

Nearly 20 years ago, Manary tested a special food rich in protein and energy (fat) that African families could feed these kids. He wanted something that wouldn’t spoil in warm weather and wouldn’t need to be cooked. It had to contain little water so that germs would not grow well in it.

“I’m an American,” he notes. “What’s in your cupboard that meets those criteria? Peanut butter!”

After Manary’s aha moment, he and his colleagues tested this idea on thousands of children who were being sent home from the hospital. He gave their mothers a paste made from peanut butter, dried milk, sugar, vegetable oil, vitamins and minerals. The bonus ingredients helped boost the paste’s nutritional value. Africans commonly eat ground peanuts, so the kids had no problem with this “medicine.” Manary told the parents to bring their kids back for regular check-ups. Each time, he checked how they were doing.

In one study with some 1,200 children, Manary compared rates of recovery in kids who had been hospitalized with severe acute malnutrition. Some were sent home and were treated with his peanut-butter mix. Others stayed in the hospital, receiving typical care. And the kids treated at home were twice as likely to recover.

Additional studies confirmed the peanut-butter therapy’s success in helping kids with severe malnutrition. Many of these kids had a type of disease called kwashiorkor (QWASH-ee-OR-kor). It’s a life-threatening condition caused by a severe shortage of protein.

Based on their success, Manary and his colleagues started a nonprofit group in 2004. They wanted to help spread their treatment plan to even more communities. Their Project Peanut Butter opened food factories in three African nations: Malawi, Sierra Leone and Ghana.

dividing cell, stem cell
This magnified cell is dividing in two. Here, the cell’s membrane is purple, and the membrane around its nucleus is blue.
Photo courtesy of Allen Institute for Cell Science

A cell’s “Google map”

To find out what proteins actually do in the body, other scientists are creating what they’re calling a “Google map of the cell.” Ru Gunawardane works in Seattle. There, she directs a stem-cell and gene-editing program at the Allen Institute for Cell Science. Her team is studying how proteins help our cells divide, move and communicate. These scientists also are making their maps of living cells and other information available to researchers elsewhere around the world.

Gunawardane’s research is aiding in the discovery of how parts of a cell all work together. She often tries to look at many cells at once to see how they and their proteins interact. Some proteins, for example, may help cells stick together while they exchange messages. “Cells love to be in a group. They have their own cliques. So how do they talk to each other?” she asks.

Proteins have another important job: managing how a cell divides. Diseases like cancer occur when cells no longer divide as they should. Instead, their “growth has gone crazy,” Gunawardane says. To better understand this, she is studying proteins in a cell’s nucleus.

She also is examining proteins that act as structural supports. These sturdy proteins keep a cell from collapsing and dying. Still other cell proteins have jobs that aren’t entirely clear. Based on advice from other scientists and studies, Gunawardane’s team is focusing on about 20 different proteins.

stem cells, dividing cells
This time-lapse video shows dividing stem cells. In each, researchers have tagged the membrane surrounding the nucleus with a fluorescent label. This glowing label is stuck to a membrane protein called LaminB1. Note how the nuclear membrane nearly disappears, then reforms within the dividing cells.

One challenge is that proteins are too small for the eye to see. To figure out how proteins work — or fail — in real life, researchers want to see how they move inside living cells. To follow their action, researchers add glowing tags to mark the proteins they’d like to track.

Each bright tag is a green fluorescent protein that jellyfish make (and that scientists often use now in their research). Gunawardane and her colleagues can attach this glowing beacon to a human protein, making it easy to spot. To look at more than one protein, the researchers sometimes tag other cells with a red fluorescent protein.

Scientists can then look through a powerful microscope to see where each glowing protein is. Gunawardane compares the method to using a tracking device to see where your dog goes. In her case, she can watch what a lit-up protein does as its cell divides, moves or “chats” with its neighbors.

Gunawardane is particularly interested in what happens as human cells grow and develop. Proteins assist in a complex process that transforms a group of cells into tissues, organs and even a whole organism.

“We’re working with stem cells, which have this amazing ability to become any cell type in the body,” she says. “We really want to know how the cell decides to stay a stem cell or become a completely different cell type.” In other words, who’s the boss that tells the cell to become a heart cell, lung cell or brain cell?

Peeking inside living cells has already revealed several surprises. One case taught Gunawardane’s team about cellular recycling. They tagged a protein attached to a membrane that surrounds — like an envelope — all the parts of a cell’s nucleus.

“I always thought that the nuclear envelope completely goes away when the cell is dividing,” she says. Instead, her team saw that some of the envelope stays intact. That way, both new cells can reuse the leftovers to help stitch together membranes to cover their new nuclei.

cell nucleus
Researchers can use glowing tags to label cell parts. The nuclear membrane here is blue (tagged with green fluorescent protein) while the cell membrane is yellow.
GIF courtesy of Allen Institute for Cell Science

If scientists know which proteins help make key decisions, Gunawardane says, they can ask which ones are misbehaving in sick cells. That knowledge could lead to new drugs that lessen or prevent errors by the sick cells.

“I was always curious about what goes wrong in disease,” she says. Even though mistakes in our genes may trigger the damage, she realized, our proteins are what do the harm. Whether they’re missing, damaged or excessive, proteins can be the difference between sickness and health.

Proteins, then, could help shape the future of medicine. Along with helping kids in the present and revealing dinosaur secrets from the past, these mini-machines are proving their mighty power.

Power Words

(for more about Power Words, click here)

acute     An adjective to describe conditions, such as an illness (or its symptoms, including pain), that typically are short in duration but severe.

amino acids     Simple molecules that occur naturally in plant and animal tissues and that are the basic building blocks of proteins.

biology     The study of living things. The scientists who study them are known as biologists.

blood vessel     A tubular structure that carries blood through the tissues and organs.

cancer     Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.

cartilage     A type of strong connective tissue often found in joints, the nose and ear. In certain primitive fishes, such as sharks and rays, cartilage provides an internal structure — or skeleton — for their bodies.

cell     The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall.

chemical     A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O.

chemistry     The field of science that deals with the composition, structure and properties of substances and how they interact. Scientists use this knowledge to study unfamiliar substances, to reproduce large quantities of useful substances or to design and create new and useful substances.

clique     A tight-knit group of individuals, often purposefully excluding others, that develops based on some common interests, attitudes, behaviors or other bond.

collagen     A fibrous protein found in bones, cartilage, tendons and other connective tissues.

colleague     Someone who works with another; a co-worker or team member.

component     Something that is part of something else (such as pieces that go on an electronic circuit board or ingredients that go into a cookie recipe).

criteria     (sing. criterion) The standards, rules, traits or other things used to make a judgment or determination about something.

defense     (in biology) A natural protective action taken or chemical response that occurs when a species confront predators or agents that might harm it. (adj. defensive)

develop    (in biology) To grow as an organism from conception through adulthood, often undergoing changes in chemistry, size and sometimes even shape.

diet     The foods and liquids ingested by an animal to provide the nutrition it needs to grow and maintain health.

digest     (noun: digestion) To break down food into simple compounds that the body can absorb and use for growth.

dinosaur     A term that means terrible lizard. These ancient reptiles lived from about 250 million years ago to roughly 65 million years ago. All descended from egg-laying reptiles known as archosaurs. Their descendants eventually split into two lines. For many decades, they have been distinguished by their hips. But a new 2017 analysis now calls into question that characterization of relatedness based on hip shape.

dissolve     To turn a solid into a liquid and disperse it into that starting liquid.

DNA     (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

doctoral degree     Also known as a PhD or doctorate, it is an advanced degree offered by universities — typically after five or six years of study — for work that creates new knowledge. People qualify to begin this type of graduate study only after having first completed a college degree (a program that typically takes four years of study).

environment     The sum of all of the things that exist around some organism or the process and the condition those things create. Environment may refer to the weather and ecosystem in which some animal lives, or, perhaps, the temperature and humidity.

extinct     An adjective that describes a species for which there are no living members.

fluorescent     (v. fluoresce) Adjective for something that is capable of absorbing and reemitting light. That reemitted light is known as fluorescence.

football field     The field on which athletes play American football. Owing to its size and familiarity, many people use this field as a measure of how big something is. A regulation field (including its end zones) runs 360 feet (almost 110 meters) long and 160 feet (almost 49 meters) wide.

fossil     Any preserved remains or traces of ancient life. There are many different types of fossils: The bones and other body parts of dinosaurs are called “body fossils.” Things like footprints are called “trace fossils.” Even specimens of dinosaur poop are fossils. The process of forming fossils is called fossilization.

gene     (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

gene editing     The deliberate introduction of changes to genes by researchers.

germ     Any one-celled microorganism, such as a bacterium or fungal species, or a virus particle. Some germs cause disease. Others can promote the health of more complex organisms, including birds and mammals. The health effects of most germs, however, remain unknown.

helix     An object with a three-dimensional shape like that of a wire wound uniformly in a single layer around a cylinder or cone, as in a corkscrew or spiral staircase.

infection     A disease that can spread from one organism to another. It’s usually caused by some type of germ.

malnutrition     (adj. malnourished) A condition that develops when an individual gets too little energy (calories) and/or not enough of the proper nutrients to support growth and health. Malnutrition can lead to stunted growth and susceptibility to disease.

mammal     A warm-blooded animal distinguished by the possession of hair or fur, the secretion of milk by females for feeding their young, and (typically) the bearing of live young.

membrane     A barrier which blocks the passage (or flow through) of some materials depending on their size or other features. Many serve that same function as the outer covering of cells or organs of a body.

microscope     An instrument used to view objects, like bacteria, or the single cells of plants or animals, that are too small to be visible to the unaided eye.

mineral     Crystal-forming substances that make up rock, such as quartz, apatite or various carbonates. (in physiology) The same chemicals that are needed by the body to make and feed tissues to maintain health.

molecule     An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).

muscle     A type of tissue used to produce movement by contracting its cells, known as muscle fibers. Muscle is rich in protein, which is why predatory species seek prey containing lots of this tissue.

nucleus     Plural is nuclei. (in biology) A dense structure present in many cells. Typically a single rounded structure encased within a membrane, the nucleus contains the genetic information.

nutrition    (adj. nutritious) The healthful components (nutrients) in the diet — such as proteins, fats, vitamins and minerals — that the body uses to grow and to fuel its processes. A scientist who works in this field is known as a nutritionist.

organ     (in biology) Various parts of an organism that perform one or more particular functions. For instance, an ovary is an organ that makes eggs, the brain is an organ that makes sense of nerve signals and a plant’s roots are organs that take in nutrients and moisture.

organism     Any living thing, from elephants and plants to bacteria and other types of single-celled life.

paleontologist     A scientist who specializes in studying fossils, the remains of ancient organisms.

peanut     Not a true nut (which grow on trees), these protein-rich seeds are actually legumes. They’re in the pea and bean family of plants and grow in pods underground.

pediatrician     A field of medicine that has to do with children and especially child health. A doctor who works in this field is known as a pediatrician.

protein     A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.

recycle     To find new uses for something — or parts of something — that might otherwise be discarded, or treated as waste.

sauropod     A very large, four-legged, plant-eating dinosaur with a long neck and tail, small head and massive limbs.

solution     A liquid in which one chemical has been dissolved into another.

species     A group of similar organisms capable of producing offspring that can survive and reproduce.

spectrometer     An instrument that measures a spectrum, such as light, energy, or atomic mass. Typically, chemists use these instruments to measure and report the wavelengths of light that it observes. The collection of data using this instrument, a process is known as spectrometry, can help identify the elements or molecules present in an unknown sample.

stem cell     A “blank slate” cell that can give rise to other types of cells in the body. Stem cells play an important role in tissue regeneration and repair.

tag     (in cell biology) The attachment of a chemical that stains a cell (or cell part) or that glows when a certain wavelength of light hits it.

tissue     Made of cells, any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms.

Tyrannosaurus rex     A top-predator dinosaur that roamed Earth during the late Cretaceous period. Adults could be 12 meters (40 feet) long.

vitamin     Any of a group of chemicals that are essential for normal growth and nutrition and are required in small quantities in the diet because either they cannot be made by the body or the body cannot easily make them in sufficient amounts to support health.

widget     In computer science, a tool built into a program or website that lets a user take action in response to information provided on screen.

Citation

Journal: E.R. Schroeter et al. Expansion for the Brachylophosaurus canadensis collagen I sequence and additional evidence of the preservation of Cretaceous protein. Journal of Proteome Research. Vol. 16, January 2017, p. 920. doi: 10.1021/acs.jproteome.6b00873.

Journal: Z. Linneman et al. A large-scale operational study of home-based therapy with ready-to-use therapeutic food in childhood malnutrition in Malawi. Maternal & Child Nutrition. Vol. 3, July 2007, p. 206. doi: 10.1111/j.1740-8709.2007.00095.x

Journal: M.A. Ciliberto et al. Comparison of home-based therapy with ready-to-use therapeutic food with standard therapy in the treatment of malnourished Malawian children: a controlled, clinical effectiveness trial. The American Journal of Clinical Nutrition. Vol. 81, April 2005, p. 864.