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Nerdy Jobs: Protein Crystallization, High school

Video of ice crystals spreading across a freezing soap bubble

Proteins are tiny parts that do jobs inside your body, and one protein is much too small to see with your eyes.

Could scientists grow a crystal, the kind you can see, out of a protein?

Nerdy Jobs S1E1, Exploring the Magic of Protein Crystallization

Dr. Raven spends a day growing protein crystals with Dr. Sarah Bowman in Buffalo, New York. A robot sets out drops too small to see, and some drops grow crystals within hours. Dr. Bowman explains that X-rays aimed at a protein crystal help scientists learn the protein’s shape and design medicines.

A NASA scientist uses a pipette to add protein solution to a crystal-growing tray at her lab bench

Meet the scientist

Dr. Sarah Bowman

  • Job titleStructural biologist. Dr. Bowman directs the National High-Throughput Crystallization Center at the Hauptman-Woodward Medical Research Institute (HWI) in Buffalo, New York.
  • A workdayThe center screens proteins for over 2,000 labs. Robots set each protein sample against 1,536 different chemical mixtures, and imagers photograph the drops for six weeks. Dr. Bowman’s own lab works on ways to grow and find tiny crystals, and uses X-ray crystallography to study proteins that hold metals.
  • TrainingA bachelor’s degree in English literature and women’s studies, then a second bachelor’s degree in chemistry. A Ph.D. in chemistry from the University of Rochester in 2010. Seven years of research at MIT and Los Alamos National Laboratory after her Ph.D.
Black-and-white photo of an early lab machine for making X-ray diffraction patterns of crystals
Photography means “drawing with light.”

Your word of the day is

kris-tuh-LOG-ruh-fee

crystallo-clear ice, rock crystalfrom Greek krýstallos
-graphydrawing, writing, recordingfrom Greek -graphía

The science of crystals and how they form.

A researcher studies a 3D model of the insulin protein on a computer screen

A protein starts as a chain of amino acids, and the order of amino acids comes from a gene.

Which chain of steps links a gene to the job a protein does?

A 3D computer model of the hemoglobin protein, drawn as a dotted surface in blue, teal and red

Hemoglobin has one shape with oxygen bound and a slightly different shape without oxygen.

Why would a structural biologist want structures of hemoglobin both with and without oxygen?

Video of an automated lab machine with a row of tubes over a sample plate

X-ray crystallography relies on many copies of a protein lined up in the same direction inside a crystal.

Why would a flexible protein be hard to study with X-ray crystallography?

A CDC illustration of the coronavirus that causes COVID-19, a gray ball covered in red spikes

Nirmatrelvir, a COVID-19 drug, was designed from X-ray structures of the main protease with another drug bound.

Why would drug designers want structures of the SARS-CoV-2 main protease with a drug bound?

Microscope view of a blood sample with round red blood cells and a few long, curved sickle cells

Claim, evidence, reasoning

In sickle cell hemoglobin, a change in the hemoglobin gene swaps one amino acid.

Which claim about sickle cell hemoglobin is best supported?

Black-and-white microscope photo of many round red blood cells

Claim, evidence, reasoning

Which evidence backs the claim that one gene change changes what hemoglobin does?

A scientist in a lab coat holds a colorful plastic model of DNA bases

Claim, evidence, reasoning

Which reasoning connects the swapped amino acid in sickle cell hemoglobin to the sickled red blood cells?

Two scientists line up a lysozyme crystal, a protein from egg whites, for an X-ray study

Dr. Bowman’s center runs lysozyme as a control in its monthly screening runs.

Why would a crystallization center test lysozyme each month when scientists already know lysozyme grows crystals?

The X-ray station at a synchrotron where scientists study protein crystals, with a robot arm that loads samples

Dr. Bowman says the more scientists know about what things look like, the better they understand how they work.

Which order of steps leads from a protein in a drop to a medicine that blocks the protein?

Two NASA scientists check a protein crystal on a diffractometer, a machine that aims X-rays at crystals

Lesson complete

Today’s word

crystallography

kris-tuh-LOG-ruh-fee

The science of crystals, how they form and how their parts are arranged.

Back to the lessonStart over
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Sources
  1. Raven Baxter, #NerdyJobs S1E1: Exploring the Magic of Protein Crystallization, YouTube, unlisted
  2. Episode transcript, with times from the episode’s YouTube captions
  3. Luft and others, Expert Opinion on Drug Discovery, 2011
  4. Lynch and others, Acta Crystallographica Section D, 2023
  5. Budziszewski and others, Journal of Visualized Experiments, 2023
  6. Ghosh and others, European Journal of Medicinal Chemistry, 2024 (nirmatrelvir and the main protease)
  7. RCSB PDB-101 Molecule of the Month: Hemoglobin (Dutta and Goodsell, 2003), Lysozyme (Goodsell, 2000), Coronavirus Proteases (Goodsell, 2020)
  8. RCSB PDB-101, Methods for Determining Atomic Structures
  9. American Crystallographic Association, Sarah Bowman candidate bio, 2023
  10. Hauptman-Woodward Medical Research Institute, news release on Dr. Bowman, 2017
  11. Vision and Change core concepts and competencies, as summarized in Brownell and others, CBE Life Sciences Education, 2014
  12. Word origins from Dictionary.com: crystallography, crystal, -graphy, protein, diffraction, calligraphy, photography, cryo-, chromatography, chromato-, graph, graphic, phonograph, lysozyme, lysosome
  13. Spanish and French spellings from Wiktionary