2022 Annual Report

A half decade of discovery: VAI’s cryo-EM turns five
To understand life’s building blocks — the molecules that give structure to our
cells, fuel our bodies and play integral roles in health and disease — we need
powerful technology that allows us to see them in deep detail.
That’s where cryo-EM comes in. Short for cryo-electron microscopy, cryo-EM is a
special type of technique and equipment that helps scientists zoom in on molecules
in their natural state. The insights gleaned from these images tell us how
molecules work, how they interact with other molecules and how they
might be leveraged to design treatments for diseases like cancer,
Parkinson’s and many others.
Five years ago, VAI established the David Van Andel Advanced
Cryo-Electron Microscopy Suite. It includes three state-of-the-art
microscopes, two of which are cryo-EM. Since then, our scientists
have made many important discoveries that are reshaping our
understanding of health and disease. To date, discoveries include:
• The first images of TRPM5, a taste-sensing molecule that may one day lead to
improved ways to treat diabetes and other metabolic and immune disorders. To
date, the structures of three of the eight proteins in this crucial molecular family
have been resolved at VAI.
• The most detailed “blueprints” to date of the mechanisms used by tuberculosis
bacteria to survive attacks by the immune system.
Around
the
Institute
• The first atomic-level images of a “molecular machine” that installs
proteins on cell membranes, a crucial process that has implications
for a host of diseases, including Alzheimer’s and cystic fibrosis.
• The first images of a special type of molecular “gate” that lets
chemical messages in and out of cells while helping them maintain
pH balance — a critical function that keeps cells alive and helps
prevent stroke and other brain injuries.
RESEARCH
• New insights into how our genetic code is repaired, a crucial process
that keeps us healthy and staves off disease.
• The first high-resolution images of a pair of molecules, DNMT3A
and DNMT3B, that play important roles in cancer and may serve as powerful
targets for anti-cancer medications.
“Cryo-EM is one of the most important
tools in modern science. It is fueling
discovery here at VAI and around the world
by sparking new advances and laying the
foundations for new frontiers in health.”
— Dr. Peter A. Jones, Chief Scientific Officer
Van Andel Institute
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