About Barbara Vann

Barb loves telling the story behind the science. She strives to make research findings relevant and engaging for all audiences—from the researcher in the field to the student in the classroom.

Optogenetics Sparks New Research Tools

Imagine if scientists could zap a single cell (or group of cells) with a pulse of light that makes the cell move, or even turns on or off the cell’s vital functions.

Scientists are working toward this goal using a technology called optogenetics. This tool draws on the power of light-sensitive molecules, called opsins and cryptochromes, which are naturally occurring molecules found in the cell membranes of a wide variety of species, from microscopic bacteria and algae to plants and humans. These light-reacting molecules change their shape or activity when they sense light, so they can be used to trigger cellular activity, such as turning on or off ion flow into the cell and other regulatory pathways. The ability to induce changes in cells has a broad range of practical applications, from enabling scientists to see how cells function to providing the basis for potential therapeutic applications for blindness, cancer, and epilepsy.

Opsins first gained a foothold in research about a decade ago when scientists began using them to study specific electrical networks in the brain. This research relied on channelrhodopsins, opsins that could be used to control the flow of charged ions into and out of the cell. Normally, when a neuron reaches a certain ion concentration, it is triggered to fire, but neuron firing can be changed by inserting opsins in the membrane. Neuroscientists figured out how to incorporate light-sensitive opsin proteins by inserting the opsin gene into the host’s DNA. The genetically encoded opsin proteins in the neuronal membranes could be turned on or off by shining light into the brain itself, using optical fibers or micro-LEDs, to switch on or off the flow of ions and neuron firing.

Since those early studies in the brain, the optogenetics field has come a long way. But the leap from brain cells to other cells has been challenging. Scientists first needed to find a way to deliver light into tissues deep in the body. And, unlike stationary brain cells, they needed a way to target cells that are on the move (such as immune cells). They also needed to develop a way to study not only cell networks but also individual cells and cell parts. The NIGMS-funded researchers highlighted below are among the scientists working to overcome these obstacles and are using optogenetics in new and inventive ways.

Illustration showing how bridges can be built within a cell using light-reacting molecules
Illustration shows how “bridges” can be built within a cell through the use of light-reacting molecules. The light triggers proteins to line up within the cell, making it easier to shuttle molecules between the membranes of two subcellular organelles. This optogenetic strategy is helping scientists to control cell function with a simple beam of light. Illustration courtesy of Yubin Zhou.

Building Bridges

Yubin ZhouLink to external web site of Texas A&M is using optogenetics to control the way cells communicate and to study immune cell function. In one line of research, Zhou is using light to make it easier for calcium ions to enter cells. The ions carry instructions for the cell and also help tether small cellular structures (called organelles).  Those inter-membrane tethers allow for the movement of  proteins and lipids back and forth across the cell, and are critical for sending chemical messengers to communicate information (see illustration). When this process is disrupted, it can lead to extreme changes in cell function and even cell death. Using this technology to “switch on” normal pathways enables the scientists to better understand how such processes can be disrupted.

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Taking the Guesswork Out of Pain Management

How do you measure pain? A patient’s furrowed brow, a child’s cries or tears—all are signs of pain. But what if the patient suffers from severe dementia and can’t describe what she is feeling or is a young child who can’t yet talk? Caregivers can help read the signs of pain, but their interpretations may differ greatly from patient to patient, because people have different ways of showing discomfort. And when the patient is unconscious, such as during surgery or while in intensive care, the caregiving team has even fewer ways to measure pain.

Pain scale--0 for no hurt to 10 for hurts worst.
Patients can point to one of the faces on this subjective pain scale to show caregivers the level of pain they are experiencing. Credit: Wong-Baker Faces Foundation.

Assessing pain is an inexact science. It includes both subjective and objective measures. A patient might be asked during a subjective assessment (performed, perhaps, with a caregiver showing a pain-rating scale such as the one in the figure), “How much pain are you feeling today?” That feedback is coupled with biological markers such as an increased heart rate, dilated pupils, sweating, and inflammation as well as blood tests to monitor high levels of the stress hormone cortisol. Combined, these measurements can give doctors a fairly clear picture of how much pain a patient feels.

But imagine if members of the surgical or caregiving team could actually “see” how the patient is feeling? Such insight would let them select better drugs to use during and after surgery, tailoring care to each patient. That tool could be put into service in the operating room and by the bedside in intensive care, giving nonstop reports of pain as the patient experiences it.

An objective measure of pain also has uses beyond the operating room and intensive care unit. Given the high risk for opioid misuse, such a measure could take the guesswork out of pain management and give doctors a more accurate indication of pain levels to prevent over-prescribing opioid pain relievers. Continue reading