Professor Erin Schuman won the Brain Prize in 2023, together with Christine Holt and Michael Greenberg “for their pioneering research into the molecular mechanisms that regulate the neural proteome during brain development, plasticity, and disease”.

The Brain Prize is an international award that recognizes and celebrates highly original and groundbreaking advances in any area of brain research, from basic neuroscience to applied clinical research. Since it was founded in 2011 and up until 2025, The Brain Prize has been awarded to 49 scientists from 11 countries.

Neurons: The Brain’s Amazing Communication Network

The brain is a fascinating control system that manages all the body’s functions, and it is made of several types of cells. In this article, we will focus on neurons—the brain cells that send and receive information through electrical and chemical messages. Your brain contains about 86 billion neurons—more than ten times the number of people living on Earth! Each neuron has three main parts (Figure 1): the cell body (the neuron’s “headquarters”), an axon—a long cable that sends messages to other neurons, and dendrites that branch out like tree limbs to receive messages from other neurons.

When an axon from one neuron meets a dendrite from another, they create a connection called a synapse. Besides transmitting info from one neuron to another, synapses are where learning happens and memories form. Each neuron typically creates thousands of synapses with neighboring neurons, building a highly connected network where information flows between them (to learn more about synapses and the communication between neurons, read this article).

Right now, as you are reading these lines, synapses in your brain are transmitting information and maybe even changing their strength and forming new connections in active brain areas. When these changes are maintained over time, they become the memories that let you recall what you have learned. So your brain is constantly changing itself, creating new connections, destroying unimportant ones, and actively maintaining the important ones.

Where Do All the Proteins Come From?

To do their incredible work—sending, receiving, and storing information—synapses need proteins. Think of proteins as biological “workers” that handle the important jobs throughout your brain and body. At synapses, proteins help build and maintain the proper structure, and they adjust synapse strength to allow learning and memory formation.

Inside cells, proteins are made in tiny factories called ribosomes (to learn more about ribosomes, read this article). In most body cells, ribosomes cluster around the nucleus, in the cell body. When a new protein is needed, ribosomes build it using a “recipe” carried by a molecule called mRNA—like following instructions to assemble a piece of furniture.

A Puzzle That Changed My Research

When I started my lab at Caltech in the 1990s, scientists believed nerve cells worked like any other cell—making all their proteins in the cell body, then shipping them out to wherever they were needed inside the cell. But there was an unsolved puzzle that made scientists question this belief: each neuron has thousands of synapses, and each synapse needs its own unique combination of proteins [1]. How could one central factory in the cell body possibly provide the exact combination of proteins that each of its thousands of synapses requires? This would be like asking one shoe factory in your neighborhood to make customized shoes for every person in town, on demand, 24/7. An almost impossible challenge!

From Memories to Proteins

I stumbled onto this protein production riddle by accident—which is how some of the best scientific discoveries happen! Originally, I was studying how memories form in the brain [2], and at that time scientists were debating whether making new proteins was important for creating new memories. My team made an important discovery: when memories formed, new proteins were immediately needed at the synapses [3]. Surprisingly, when we removed the cell bodies from our experiments and studied isolated synapses, these new proteins still were still apparent!

The only logical conclusion was that the protein-making machinery had to be very close to the synapses we were measuring [4]. Might neurons have local protein factories near their synapses, completely separate from those in the cell body? This surprising and fascinating discovery shifted my entire research program, and to this day this question is still my main research topic.

All About the Click

At first, we could not measure proteins and mRNAs with enough accuracy to solve the riddle. We had to tag newly made proteins near synapses with dangerous radioactive materials–substances that give off invisible energy, which can sometimes be harmful—and that gave us uncertain results. Luckily, my chemistry colleague Dave Tirrell, at Caltech, started developing a brilliant new way to tag proteins using non-radioactive chemical groups. The core of this method was that two matching chemical groups are naturally attracted to each other—when they meet, they “click” together like strong magnets, forming a stable connection [5]. This method is called click chemistry.

Dave’s lab and my lab used click chemistry to tag newly made proteins in neurons [6], which allowed us to capture and separate those proteins from old ones, and even see them directly under powerful microscopes. Suddenly, we could detect 5,000 different proteins in neurons, about 25 times more than before! These new methods confirmed what we suspected: proteins are made along axons and dendrites too, not just in cell bodies. We had discovered a completely new model—instead of one central factory, neurons have local protein production factories that create proteins right near their synapses.

Proteins On-Demand

Today we know that every single synapse contains about 500 different types of proteins, with roughly 50 copies of each type—that is about 25,000 proteins per synapse! Some protein copies are made in the cell body and shipped out, while others are produced locally, right near the synapse. But how does the neuron coordinate this split production system?

Like most things in biology, the answer is not simple, but we have started to define the process. The central “factory” in the cell body has a higher production capacity than the tiny local factories near synapses (Figure 2). So it makes sense that when cells need to build complex biological machines made of many different protein parts, most of the heavy construction happens in the cell body, while smaller, customized pieces get made locally.

Think of it like car manufacturing: the big factory makes the major components—the frame, doors, and engine—then ships them to smaller factories. At these local factories, custom parts are added, like tires, windows, and stereo systems. This works for synapses because they are constantly changing and need frequent on-demand customization. This split production system makes protein production flexible. Sometimes it is better to make more of a specific protein locally, at the synapse; other times, central production is more efficient.

The Brain’s Delivery System

The central and local protein factories in neurons are connected through a very sophisticated supply system that moves mRNA molecules and newly made proteins along cellular “highways” connecting cell bodies to synapses (Figure 3) [1]. These highways allow two-way communication, so synapses can also send signals back, to tell the cell body which proteins they need next.

Even with today’s advanced methods, it is incredibly challenging to zoom in on a single synapse to see exactly what is happening there. We are still working on unanswered scientific questions, including: How many protein copies are made right at the synapse vs. adjacent regions on dendrites and axons? Do synapses share mRNAs and ribosomes with their neighbors—like one maintenance team at your school taking care of several classrooms?

Although these and other questions remain, one thing is clear: the brain developed a production and delivery system that is at least as sophisticated as the most advanced delivery systems humans have ever built! Each neuron produces and delivers hundreds of millions of proteins every day. This is exactly why I find this field so fascinating—we are uncovering biological “technologies” that leave us in awe of what nature has accomplished!

Glossary

Neurons: ↑ Brain cells that communicate through electrical and chemical signals, forming the networks that control everything the body does.

Axon: ↑ The neuron’s “transmission cable” that carries electrical messages away from the cell body to other neurons.

Dendrites: ↑ The neuron’s “receivers” which branch out like tree limbs to collect incoming messages from other neurons.

Synapse: ↑ The connection “junction” where the axon of one neuron meets a dendrite from another neuron. This is where learning happens and memories form.

Proteins: ↑ Large molecules built from smaller building blocks. They fold into specific shapes to do jobs in cells, such as building structures, sending signals, and transporting materials.

Ribosomes: ↑ Tiny protein “factories” that read mRNA instructions and build proteins from them.

mRNA: ↑ Messenger RNA, the molecule that carries the instructions ribosomes read to make specific proteins.

Click Chemistry: ↑ A chemical method used to accurately tag and study molecules in cells. It uses two matching chemical groups that “click” together, allowing scientists to isolate and see single molecules.

Conflict of Interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

I wish to thank Or Raphael for conducting the interview that served as the basis for this paper, and for co-authoring the paper, Iris Gat for providing the figures, and Susan Debad for copyediting the manuscript.

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