Every living thing on Earth carries a molecular instruction manual inside its cells, called DNA. DNA stands for deoxyribonucleic acid, and it is a long, double-stranded molecule twisted into a double helix—a breakthrough discovery in 1953, made in part by Nobel Laureate Francis Crick, a founding Nonresident Fellow at Salk.
Stretched end to end, the DNA packed into a single human cell would measure about six feet, but it’s coiled so tightly it fits inside a space far smaller than the eye can see. DNA is organized into sections called genes, each carrying the instructions to build specific proteins. The “language” of DNA is only four letters: A (adenine), T (thymine), C (cytosine), and G (guanine). Each of these letters represents a different chemical base used to build the DNA strand and the many genes it contains.
The way DNA is coiled in 3D space and additional chemical tags on top of the base code determine which genes get used in any given cell; this is how one set of instructions can be used to make specialized cells for the immune system, brain, heart, skin, and everywhere else in the body.
Salk researchers are dedicated to understanding and cataloging this essential code. They create reference atlases of the A-T-C-G base code in model animals and humans; they study how the 3D architecture of DNA changes its activity; and they pinpoint which mutations and misuses of DNA lead to diseases and disorders.
Ribonucleic acid (RNA) carries genetic instructions from DNA out of the nucleus and into the cell body, where it can be read and translated into proteins. Like DNA has its characteristic A, T, C, G, building blocks, RNA has its own letters, each standing for a different chemical base used to build the RNA strand: A (adenine), U (uracil), C (cytosine), and G (guanine). RNA can fold into complex shapes, catalyze chemical reactions, and regulate which genes are used, when.
There are many types of RNA, each with a different job: messenger RNA carries the protein-building instructions, transfer RNA assembles the protein piece by piece, and small regulatory RNAs can silence genes entirely.
The COVID-19 vaccines brought RNA into public conversation in a new way, harnessing the molecule’s protein-building ability as a therapeutic tool. This innovation is just a glimpse of the broader revolution in RNA-based medicine now underway.
Epigenetics is the set of “instructions on top of DNA” that helps your cells decide which genes to use, when to use them, and how strongly to use them—without changing the letters of the DNA itself. A helpful way to picture it is a cookbook: Nearly every cell in your body carries the same cookbook (your genome), but a brain cell and a muscle cell don’t make the same “recipes.”
Epigenetic marks are like sticky notes, bookmarks, and page clips that tell each cell which recipes to open, which to keep closed, and which to make more often. These marks help guide development, for example, how one fertilized egg becomes many different cell types. These instructions can shift over time as our bodies grow and age.
At Salk, scientists study epigenetic regulators to understand how cells turn genes “on” and “off” in precise patterns—and what happens when those patterns go off course in conditions like cancer and immune disorders. Others map epigenetic changes in plants to understand how genes respond to stress, with the long-term goal of supporting crop resilience through traits such as drought tolerance.
CRISPR gene editing is a technique that scientists use to cut out genes in cells and observe what happens next. CRISPR (adapted from a bacterial defense system) is like a GPS-guided pair of scissors for DNA. A short “guide” molecule leads a cutting protein (often Cas9) to a specific genetic address, and the DNA is cut at that spot. Then the cell’s own repair crew steps in. Depending on how the repair is performed—and whether researchers provide replacement code to copy—the edit can disable a gene or introduce a precise change.
Why does that matter? Because it lets scientists ask clear, foundational questions: What does this gene do, and what changes when we tweak it? Multiply that by thousands of genes, and CRISPR becomes a discovery engine for mapping the hidden circuitry of biology.
At Salk, researchers use CRISPR screening to sift through thousands of fat-cell genes to uncover previously overlooked microproteins that influence lipid storage—opening new starting points for future therapies to treat obesity and related metabolic disorders.
There are tens of billions of neurons in your brain, each zapping information around to facilitate life—walking, talking, remembering, cooking, eating, and everything else the body needs. The physical form of each neuron is shaped by its function: branching appendages that receive messages, called dendrites; a central cell body that processes that information; and an outstretched arm that sends messages, called an axon. Where two neurons meet is called a synapse, and these synaptic connections constitute the sprawling networks of connectivity throughout the brain.
Salk scientists have been and continue to make significant contributions to neuronal research. For example, Rusty Gage, PhD, discovered that our brains can make neurons throughout our lifetimes—overturning a long-held belief that the neurons we are born with are all we get. Today, our researchers study how neurons form and function across a lifetime, what happens when they disconnect from one another or malfunction independently, and what lifestyle or therapeutic interventions can stave off neurological disorders and diseases.
Neurons have taken the spotlight in neuroscience research for quite a while—but they aren’t the only cells in our brains. Working alongside neurons in the brain is a class of support, scaffolding, and repair cells called glia. There are roughly as many glia in the brain as there are neurons, and one of the most abundant glial cells is the astrocyte.
Astrocytes get their space-sounding name from their star-like shape: a cell body with many arms reaching out in all directions. One single astrocyte can support up to one million neuronal connections in the human brain. Each astrocyte performs the critical work of clearing excess chemical messengers released during neuron-to-neuron communication, recycling those molecules, and ensuring the brain environment is conducive to healthy neuronal activity. Researchers at Salk are bringing astrocytes center-stage—giving them the spotlight when asking questions about aging, neurodevelopmental disorders, and neurological diseases.
While half of the brain is made up of the familiar neurons, the other half is made up of cells called glia. Within this glia subtype of brain cells are microglia—resident immune cells in the brain that also carry out the important work of pruning unnecessary or redundant connections in the developing brain. Microglia are constantly surveying the brain environment, ensuring that intruders and illness stay at bay and the brain’s critical neuronal connections are protected.
Salk scientists are exploring how these brain-resident immune cells keep brains healthy throughout our lifetimes, what happens when they malfunction, and whether there are ways to repair them when they fail.
Neurons are constantly talking to one another, often across tiny gaps between them, called synapses. At these junctions, information must jump across open space. Neurotransmitters are the chemical messengers that make that leap.
Released from one neuron and received by the next, they carry signals that tell the receiving cell to fire, slow down, or change its activity. Familiar names like dopamine, serotonin, and glutamate are all neurotransmitters, each with distinct roles in shaping mood, movement, memory, and more. When neurotransmitter systems fall out of balance, the consequences ripple outward into conditions like depression, Parkinson’s disease, and addiction. Studying neurotransmitters is part of the groundwork for understanding how the brain functions and malfunctions, including in cognitive decline and neurological diseases.
Every cell in your body is constantly receiving information from its environment through chemical signals, physical cues, and messages from neighboring cells, then deciding how to respond. A cell signaling pathway is the chain of molecular events that occur after an external or internal signal—a hormone, a molecule, a virus—pops up in a cell or on its surface, ultimately triggering a change in the cell’s behavior or gene activity.
After the signal is recognized, it gets handed off to a series of proteins until it eventually reaches its destination where the actual work gets done—turning a gene on or off, prompting a cell to divide, or triggering a cell to self-destruct, for example. When these pathways are disrupted, cells can start behaving erratically, which underlies many cancers, immune disorders, and neurodegenerative diseases.
Inside every cell is a bustling world of reactions and interactions that need to be switched on and off to stay consistent with changing demands. Kinases are a family of proteins that attach a small chemical tag called a phosphate group to other proteins to change how they behave, for example, switching them on or off.
This process, called phosphorylation, is one of the most common ways cells regulate a protein’s internal machinery. A single kinase can affect dozens of downstream targets, making kinases central in everything from cell growth and metabolism to immune responses and brain function.
Mutations in kinases are found across a wide range of diseases, and researchers have found promise in targeting kinases for drug development. The therapeutic potential for kinases is especially clear in the work of Salk scientist Tony Hunter, PhD, who discovered tyrosine phosphorylation by tyrosine kinases is an effective target for cancer drugs. His discovery has resulted in the development of 100+ cancer drugs that inhibit tyrosine kinases, helping millions of patients worldwide.