How the Society of General Physiologists Unlocks Cellular Secrets
What if the most profound secrets of life are hidden in the microscopic gates that control the flow of tiny particles in and out of our cells? This is the fundamental question that has driven the Society of General Physiologists (SGP) since its founding in 1946.
For nearly eight decades, this unique scientific community has served as a home for researchers dedicated to understanding the universal mechanisms of life—from the rhythmic beating of our hearts to the electrical firing of our neurons.
At the heart of their mission lies a simple truth: the most complex biological phenomena often stem from elegantly simple physical and chemical principles governing how cells interact with their environment. Through pioneering experiments and collaborative discovery, SGP scientists continue to reveal how the carefully choreographed movement of ions across cellular membranes underpins everything from our thoughts to our heartbeats.
Studying the microscopic gates that control cellular communication
Exploring fundamental processes common across diverse life forms
Breaking down barriers between scientific disciplines
Founded at the Marine Biological Laboratory in Woods Hole, Massachusetts, the Society of General Physiologists emerged from a revolutionary idea: to break down the artificial barriers between plant and animal physiologists and create a space where scientists of different backgrounds could unite to explore the universal mechanisms of life 4 7 .
Under the leadership of visionaries like R. Chambers, E. N. Harvey, L. V. Heilbrunn, and M. H. Jacobs, the Society established itself as a cradle for interdisciplinary collaboration 7 .
Unlike specialized organizations focused on particular organs or systems, SGP has dedicated itself to "general physiology"—the study of fundamental processes common across diverse life forms. As their archives at the National Library of Medicine document, the Society's founding purpose was "to promote and advance the subject of general physiology and to provide a structure for general physiologists of different training and backgrounds to meet and exchange ideas" 7 .
This commitment to cross-disciplinary dialogue has made SGP particularly influential in fields like membrane transport and ion channels, cell membrane structure, cellular contractility, and molecular motors 4 .
Approximately 600 career physiologists working across academia, government, and industry 4
Supporting promising early-career researchers through awards like SGP Scholars @MBL 5
Creating spaces for scientists from different backgrounds to exchange ideas and collaborate
In 2024, the SGP recognized a groundbreaking study with its prestigious Paul F. Cranefield Award, presented to Huanghe Yang for research revealing how a common medication could unexpectedly affect blood vessel constriction 1 .
The study, published in the Journal of General Physiology, investigated the interaction between Niclosamide (a drug used to treat parasitic infections) and the TMEM16A channel—a protein that facilitates chloride ion movement across cell membranes.
The discovery was both surprising and significant: Niclosamide, rather than blocking the TMEM16A channel as might be expected, actually potentiated its activity, leading to increased vasoconstriction (narrowing of blood vessels) 1 .
This finding was particularly noteworthy because TMEM16A channels play crucial roles in various physiological processes, including neuronal activity, cardiovascular tone, and secretion from glands. Understanding how drugs affect these channels is essential for developing safer medications and targeted therapies for conditions like chronic pain, epilepsy, and cardiovascular diseases.
| Award Category | Recipient | Research Focus |
|---|---|---|
| Paul F. Cranefield Award | Huanghe Yang | "Niclosamide potentiates TMEM16A and induces vasoconstriction" |
| Cranefield Postdoctoral Fellow Award | Man Si | "Epilepsy-associated Kv1.1 channel subunits regulate intrinsic cardiac pacemaking in mice" |
| Cranefield Student Award | Rachael Lucero | "Transport of metformin metabolites by guanidinium exporters of the small multidrug resistance family" |
The research team employed a sophisticated multi-step approach to unravel the complex relationship between Niclosamide and TMEM16A channels:
Researchers first isolated TMEM16A channels in controlled laboratory systems to study their function without interference from other cellular components.
Using patch-clamp electrophysiology—a technique that measures ionic currents across cell membranes—the team precisely quantified chloride movement through TMEM16A channels under various conditions.
The researchers applied Niclosamide to the isolated channels and measured changes in chloride ion flow, expecting the drug to inhibit channel activity based on its known effects on other biological targets.
To connect molecular findings to tissue-level effects, the team examined how Niclosamide affected isolated blood vessels, carefully measuring changes in vessel diameter using specialized imaging equipment.
The researchers conducted parallel experiments using specific TMEM16A inhibitors to confirm that the observed effects were indeed mediated through this specific channel and not through other mechanisms.
This systematic approach allowed the team to move confidently from molecular interactions to physiological consequences, establishing a clear cause-effect relationship between Niclosamide, TMEM16A potentiation, and vasoconstriction.
The findings challenged conventional expectations and revealed new complexities in drug-channel interactions:
Contrary to initial hypotheses, Niclosamide enhanced TMEM16A channel activity rather than suppressing it. The channels demonstrated increased chloride conductance in the presence of the drug.
The potentiation effect showed concentration dependence—higher doses of Niclosamide produced greater enhancement of channel activity, up to a maximum effect.
This TMEM16A potentiation translated directly to physiological changes, with blood vessels showing significant constriction when exposed to Niclosamide.
The research suggested that TMEM16A activity must be carefully considered when using Niclosamide, particularly in patients with cardiovascular conditions, and pointed to potential new applications for modified versions of the drug.
| Experimental Parameter | Observed Effect | Physiological Significance |
|---|---|---|
| TMEM16A chloride current | Increased by Niclosamide | Enhanced channel opening probability |
| Blood vessel diameter | Significant decrease | Notable vasoconstriction |
| Response to TMEM16A inhibitors | Blocked Niclosamide effect | Confirmed TMEM16A-specific mechanism |
| Dose-response relationship | Concentration-dependent effect | Suggests clinical relevance at therapeutic doses |
The scientific importance of these findings lies in their demonstration that drug effects can be full of surprises. A medication known primarily for one biological action (anti-parasitic effects) can have unexpected, opposite effects on different cellular targets. This research emphasized the critical importance of understanding off-target effects and provided new insights into how existing drugs might be repurposed for new therapeutic applications.
Modern physiology research relies on sophisticated tools and reagents to probe cellular mechanisms. The following essential resources represent the core "toolkit" enabling discoveries like the Niclosamide-TMEM16A research:
| Tool/Reagent | Primary Function | Research Application |
|---|---|---|
| Tag-lite technology | Non-radioactive TR-FRET-based solution for assessing ligand/receptor interactions | Measures molecular binding events in real-time without radioactivity 6 |
| Radiolabeled ligands | Radioactive compounds that bind to specific receptors | Used in saturation, competition, and kinetic binding studies 6 |
| GPCR membrane preparations | Cell membranes enriched with specific receptor proteins | Provides consistent material for drug screening and receptor characterization 6 |
| Patch-clamp electrophysiology | Technique for measuring ionic currents across cell membranes | Studies ion channel function and regulation in real-time 1 |
| GTPγS binding assays | Measures G-protein activation | Determines whether receptors activate stimulatory or inhibitory pathways 6 |
"I study the physics that dictates the way these cells move together to achieve specific goals, and how we can modulate that behavior to better understand and assist biological functions."
The Society of General Physiologists continues to drive innovation by focusing on emerging fields where fundamental discoveries await. The upcoming 2025 SGP Annual Meeting, titled "Tracing the Path of Chloride: From Ion Channels and Transporters to Physiology and Therapeutics," exemplifies this forward-looking approach 2 .
The conference will bring together researchers working to understand how chloride channels and transporters operate at the molecular level and how their dysfunction contributes to conditions like chronic pain, epilepsy, and neurodegeneration 2 .
This focus on chloride biology represents a natural progression from discoveries like the Niclosamide-TMEM16A research, expanding our understanding of how this simple ion exerts such profound influence on health and disease.
"Coming back to research has been a daunting process... This award certainly takes some of the edge off those concerns. It's also a very nice boost to a graduate stipend."
From a surprising discovery about a common drug's effect on blood vessels to the fundamental mechanisms that keep our bodies functioning, the work supported by the Society of General Physiologists reminds us that life's complexity arises from beautifully simple principles. The careful movement of ions across microscopic cellular gates coordinates everything from our heartbeats to our thoughts, connecting diverse biological processes through a universal language of physiology.
Breaking down barriers between scientific specialties to advance understanding
Cultivating the next generation of physiology researchers
Exploring the universal processes that underlie all life forms
As we've seen through the research recognized by SGP awards and the tools developed by physiological researchers, understanding these fundamental mechanisms does more than satisfy scientific curiosity—it provides the foundation for medical advances that can improve human health.
The Society's commitment to cross-disciplinary collaboration, support for emerging scientists, and focus on fundamental mechanisms ensures that physiology will continue to reveal nature's secrets, one ion channel at a time.
As one physiology educator has noted, true understanding of physiology means being able to "use basic knowledge to perform the tasks for which it is relevant" 8 . Through its symposia, publications, and support for researchers at all career stages, the Society of General Physiologists continues to foster this deep, functional understanding of how life works at its most essential level—ensuring that the big ideas of physiology continue to energize and inspire both scientists and the public for years to come.