Noise and Signals (Archive)

Originally posted February 13, 2018.

Sam Entwisle is a PhD student who studies a calorie-burning tissue in mammals called brown fat. His research goal is to understand when and how brown fat uses this calorie-burning ability, knowledge which could ultimately improve treatment of metabolic diseases such as type-2 diabetes.

Signals are everywhere, it seems. A green light during the daily commute, the sign on a bathroom door, a clock chime. These communicate something specific, and often inspire direct action. We press the gas pedal when the stoplight turns, we open the bathroom door or else move on to the next one, we get ready for a scheduled dinner date. However, signals aren’t always so obvious. A car horn heard during rush hour may or may not be directed at us. Glances and gestures — social signals — are exchanged between our co-workers or friends with some room for interpretation. Thoughts and memories enter our mind from nowhere, like signals from past or future experiences. It can be overwhelming. How many signals can we possibly receive at once? How do we know what is a signal to us, and what is just noise?

As a cell biologist, signals fascinate me. Our body is made of trillions of cells that signal to each other all the time. Cells experience countless signals. Cells receive signals from close to 90 different hormones in the bloodstream. Cells receive signals from the brain, which fires off electric pulses that travel to cells like a landline phone call. Cells receive signals from neighboring cells in close quarters, as if in a face-to-face conversation. Cells even receive signals from within themselves, which report on things like whether they are running low on particular nutrients, or whether they are ready to multiply. To manage this barrage of information, our cells have evolved ingenious strategies. They have no other choice. Instructions delivered to cells by signals can make the difference between health and disease, or between life and death.

One important signal is the hormone insulin. After we eat a meal, cells in our pancreas release insulin into the bloodstream. From there, it rushes throughout the body and tells other cells — muscle cells, fat-storing cells, liver cells — to prepare for incoming nutrients. People with type-2 diabetes often cannot respond properly when their pancreas releases insulin, which in turn worsens the disease. Correcting faulty signaling is a promising strategy for treating type-2 diabetes. I study new ways we might do this.

How do cells receive signals? First, a hormone from the blood, or an electric pulse from the brain, arrives at a cell. The signal then gets transmitted into that cell, where it leaves marks on tiny molecular machines called proteins. In a single experiment, I measure thousands of these protein marks while giving cells different signals. The end result is a very long list. We already know that some of these protein marks help cells identify and interpret various signals. Many of the marks on my lists, however, are mysterious. Which of them help the cell interpret signals? Do my lists contain any information that will help people with type-2 diabetes? What does it all mean? After hours of staring at a list, in darker moments, it can feel like the answer to the last question is: nothing. It’s all noise.

Noise, in this sense, is something that is irrelevant or meaningless. When my list of protein marks doesn’t make sense, I worry that it contains only noise. From the perspective of a cell, some protein marks help it understand the signals it is receiving, while others may be noise. But noise can be a subjective term. What I perceive as noise might not be perceived as noise by a cell. I’m reminded of experiences listening to modern styles of jazz. For years these tunes seemed to me completely without structure, just random notes strung together. However, as I got older I began to experience some of them in new ways. The mutating rhythms and fluid melodies that initially challenged me all of a sudden made perfect sense, and ran through me like a jolt of electricity — a sort of signal. In my research, distinguishing signal from noise can be challenging, but the potential for discovery drives me forward.

Cells live in a complex and ever-changing environment. The sheer number of signals they receive at a given time might even resemble noise to an untrained eye. We scientists get better at finding meaning in our data with every passing year. But cells have always had an unparalleled ability to identify signals — many signals — in the face of noise. This allows them to keep us healthy by maintaining connections with the other cells that form and animate our bodies.