Tag: Cool Tools/Techniques

More Than 25 Years of Competition and Collaboration Advance the Prediction of Protein Shapes

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Proteins (such as hemoglobin, actin, and amylase) are workhorse molecules that contribute to virtually every activity in the body. Some of proteins’ many jobs include carrying oxygen from your lungs to the rest of your body (hemoglobin), allowing your muscles to move (actin and myosin), and digesting your food (amylase, pepsin, and lactase). All proteins are made up of chains of amino acids that fold into specific 3D structures, and each protein’s structure allows it to perform its distinct job. Proteins that are misfolded or misshapen can cause diseases such as Parkinson’s or cataracts.

While it’s straightforward to use the genetic code to predict amino acid sequences of proteins from gene sequences, the vast diversity of protein shapes and many factors that influence a protein’s 3D structure make it much more complicated to create simple folding rules that could be used to predict proteins’ structures from these sequences. Scientists have worked on this problem for nearly 50 years, and NIGMS has supported many of their efforts, including the Critical Assessment of Structure Prediction (CASP) program.

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A Focus on Microscopes: See Eye-Catching Images

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Have you ever wondered what creates striking images of cells and other tiny structures? Most often, the answer is microscopes. Many of us have encountered basic light microscopes in science classes, but those are just one of many types that scientists use. Check out the slideshow to see images researchers have captured using different kinds of microscopes. For even more images of the microscopic world, visit the NIGMS Image and Video Gallery.

Visualizing Structures

Type of Microscope: Dark field
Used to Study: Living and dead cells

Oblong bacteria glowing blue on a black background.
Anthrax bacteria being killed by an agent that naturally glows blue when excited by ultraviolet light in the microscope.
Credit: Keiler Lab, Penn State University.

Type of Microscope: Time lapse
Used to Study: Living cells as they move over time

Cell-like compartments spontaneously emerge from scrambled frog eggs, with nuclei (blue) from frog sperm. Endoplasmic reticulum (red) and microtubules (green) are also visible.
A dividing cell of an African globe lily. This is one frame of a time-lapse sequence that shows cell division in progress.
Credit: Andrew S. Bajer, University of Oregon, Eugene.

Type of Microscope: Super resolution light
Used to Study: Activity in living cells

Oblong blue structures with red threads connected to them on the left and right.
DNA (blue) being pulled apart by microtubules (red) as a cell divides. The blue and red colors are due to the fluorescent label used to dye the sample.
Credit: Jane Stout and Claire Walczak, Indiana University.

Type of Microscope: Fluorescent light
Used to Study: Activity in dyed cells and molecules

Many spots and swirls of fluorescent green and purple.
Kidney tissue stained with fluorescent dyes that glow under high intensity light from the microscope.
Credit: Tom Deerinck and Mark Ellisman, NCMIR.

Type of Microscope: Confocal
Used to Study: 3D images of living cells

Round green-yellow structures with red edges and blue dots in their centers.
Cell-like compartments that spontaneously emerge from scrambled frog eggs, with nuclei (blue) from frog sperm.
Credit: Xianrui Cheng, Stanford University School of Medicine. Xianrui Cheng, James E. Ferrell Jr. SCIENCE 366: 631, 01 Nov 2019 (DOI: 10.1126/science.aav7793).

Type of Microscope: Electron
Used to Study: Dead cells

A circle containing many types of structures an inner circle that is clear.
Cross-section through the worm, C. elegans, revealing various internal structures frozen in time. This image was taken with transmission electron microscopy and labeled afterwards with color to highlight features in the image.
Credit: Piali Sengupta, Brandeis University.

Type of Microscope: Cryo-EM
Used to Study: Cellular components, particles (viruses, molecules, ribosomes)

An oblong capsule made up of tiny gray, yellow, and red structures.
The protein shell, or capsid, that surrounds HIV and is covered in a host protein (red), which allows the virus to evade detection.
Credit: Juan R. Perilla, Klaus Schulten, and the Theoretical and Computational Biophysics Group.

Explore Scientific Imaging Through a Virtual “Internship”

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Students, teachers, and other curious minds can step into a scientific imaging lab with a free online interactive developed by NIGMS and Scholastic. Imaging tools help scientists unlock the mysteries of our cells and molecules. A better understanding of this tiny world can help researchers learn about the body’s normal and abnormal processes and lead to more effective, targeted treatments for illnesses.

Entrances to the virtual imaging labs.
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Pathways: The Imaging Issue

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Cover of Pathways student magazine showing geometric shapes, pom-pom-like structures, and text that reads, Dive into the microscopic world. What do you think this image shows? Hint: It’s NOT an underwater scene! (Answer inside). Cover of Pathways student magazine.

NIGMS and Scholastic bring you our latest issue of Pathways, which focuses on imaging tools that help scientists unlock the mysteries of our cells and molecules. A better understanding of this tiny world can help researchers learn about the body’s normal and abnormal processes and lead to more effective, targeted treatments for illnesses.

Pathways is designed for students in grades 6 through 12. This collection of free resources teaches students about basic science and its importance to health, as well as exciting research careers.

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Year in Review: Our Top Three Posts of 2020

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Over the year, we dove into the inner workings of cells, interviewed award-winning researchers supported by NIGMS, shared a cool collection of science-themed backgrounds for video calls, and more. Here, we highlight three of the most popular posts from 2020. Tell us which of this year’s posts you liked best in the comments section below!

The Science of Infectious Disease Modeling

Oblong light-blue structures with red spots in the middle connected to the surface of a sphere. Spike proteins on the surface of a coronavirus. Credit: David Veesler, University of Washington.

What does “modeling the spread” (or “flattening the curve”) mean, and how does it apply to infectious diseases such as COVID-19? Learn about the science of infectious disease modeling and how NIGMS supports scientists in the field.

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An Enlightening Protein

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A fly glowing green. A fruit fly expressing GFP. Credit: Jay Hirsh, University of Virginia.

During the holiday season, twinkling lights are a common sight. But no matter what time of the year, you can see colorful glows in many biology labs. Scientists have enabled many organisms to light up in the dark—from cells to fruit flies and Mexican salamanders. These glowing organisms help researchers better understand basic cell processes because their DNA has been edited to express molecules such as green fluorescent protein.

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Q&A With Nobel Laureate and CRISPR Scientist Jennifer Doudna

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A headshot of Dr. Doudna. Jennifer Doudna, Ph.D. Credit: University of California, Berkeley.

The 2020 Nobel Prize in Chemistry was awarded to Jennifer Doudna, Ph.D., and Emmanuelle Charpentier, Ph.D., for the development of the gene-editing tool CRISPR. Dr. Doudna shared her thoughts on the award and answered questions about CRISPR in a live chat with NIH Director Francis S. Collins, M.D., Ph.D. Here are a few highlights from the interview.

Q: How did you find out that you won the Nobel Prize?

A: It’s a little bit of an embarrassing story. I slept through a very important phone call and finally woke up when a reporter called me. I was just coming out of a deep sleep, and the reporter was asking, “What do you think about the Nobel?” And I said, “I don’t know anything about it. Who won it?” I thought they were asking for comments on somebody else who won it. And she said, “Oh my gosh! You don’t know! You won it!”

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Freezing a Moment in Time: Snapshots of Cryo-EM Research

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To get a look at cell components that are too small to see with a normal light microscope, scientists often use cryo-electron microscopy (cryo-EM). As the prefix cryo- means “cold” or “freezing,” cryo-EM involves rapidly freezing a cell, virus, molecular complex, or other structure to prevent water molecules from forming crystals. This preserves the sample in its natural state and keeps it still so that it can be imaged with an electron microscope, which uses beams of electrons instead of light. Some electrons are scattered by the sample, while others pass through it and through magnetic lenses to land on a detector and form an image.

Typically, samples contain many copies of the object a scientist wants to study, frozen in a range of orientations. Researchers take images of these various positions and combine them into a detailed 3D model of the structure. Electron microscopes allow us to see much smaller structures than light microscopes do because the wavelengths of electrons are much shorter than the wavelength of light. NIGMS-funded researchers are using cryo-EM to investigate a range of scientific questions.

Caught in Translation

One cluster that is yellow, purple, and orange and another that is beige, purple, and green. 3D reconstructions of two stages in the assembly of the bacterial ribosome created from time-resolved cryo-EM images. Credit: Joachim Frank, Columbia University.

Joachim Frank, Ph.D., a professor of biochemistry and molecular biophysics and of biological sciences at Columbia University in New York, New York, along with two other researchers, won the 2017 Nobel Prize in Chemistry for developing cryo.

Dr. Frank’s lab focuses on the process of translation, where structures called ribosomes turn genetic instructions into proteins, which are needed for many chemical reactions that support life. Recently, Dr. Frank has adopted and further developed a technique called time-resolved cryo-EM. This method captures images of short-lived states in translation that disappear too quickly (after less than a second) for standard cryo-EM to capture. The ability to fully visualize translation could help researchers identify errors in the process that lead to disease and also to develop treatments.

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Exploring Nature’s Treasure Trove of Helpful Compounds

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An oblong shell with white-and-brown markings. A cone snail shell. Credit: Kerry Matz, University of Utah.

Over the years, scientists have discovered many compounds in nature that have led to the development of medications. For instance, the molecular structure for aspirin came from willow tree bark, and penicillin was found in a type of mold. And uses of natural products aren’t limited to medicine cabinet staples and antibiotics. A cancer drug was originally found in the bark of the Pacific yew tree, and a medication for chronic pain relief was first isolated from cone snail venom. Today, NIGMS supports scientists in the earliest stages of investigating natural products made by plants, fungi, bacteria, and animals. The results could inform future research and bring advances to the field of medicine.

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Helium: An Abundant History and a Shortage Threatening Scientific Tools

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Most of us know helium as the gas that makes balloons float, but the second element on the periodic table does much more than that. Helium pressurizes the fuel tanks in rockets, helps test space suits for leaks, and is important in producing components of electronic devices. Magnetic resonance imaging (MRI) machines that take images of our internal organs can’t function without helium. And neither can nuclear magnetic resonance (NMR) spectrometers that researchers use to determine the structures of proteins—information that’s important in the development of medications and other uses.

A square showing helium’s abbreviation, atomic number, and atomic weight connected by lines to illustrations of a scuba diver, a car, and a person in an MRI machine. Helium’s many uses include helping deep sea divers breathe underwater, airbags in cars to inflate, and magnets in MRI scanners to work properly. Credit: Compound Interest.
CC BY-NC-ND 4.0 Link to external web site. Click to enlarge
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