A Nobel Prize with a connection to UB research

On Oct. 4, the Nobel Prize for Physiology or Medicine was awarded to two researchers for their work in identifying the proteins responsible for providing our ability to sense heat and touch.

These were milestones to commemorate, and well-deserved by the researchers who made the discoveries: Dr. David Julius at the University of California, San Francisco, and Dr. Ardem Patapoutian at Scripps Research in La Jolla, California.

With regard to sensing touch, Dr. Patapoutian won the prize for identifying Piezo proteins, which are a type of ion channel on the surface of cells that respond to pressure and stretching.

This can be the pressure or stretching felt as we slide our finger across the surface of a table, or the pressure in our arteries that occurs with each heartbeat. It can be the stretch felt in our lungs when we take a deep breath, or the pain felt by the inflammation caused by a mosquito bite.

The touch sensitivity award is significant to the UB community because the category of ion channels that provide this sensitivity were first observed right here in Buffalo.

Forty years ago, Dr. Frederick Sachs, SUNY Distinguished Professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB, used miniature glass pipettes to suck on the surface of skeletal muscle cells. And in so doing he recorded for the first time the tiny electrical currents that were produced by mechanosensitive ion channels that were most likely Piezo channels.

This seminal publication (Journal of Physiology, London, 1984, 352, 685-701) opened the door to the field of touch-pressure sensitivity. And this first paper was followed by many publications by Dr. Sachs and others over the next 25 years, using his technique to investigate how mechanosensitive ion channels provide many different cell types with the ability to feel their surroundings.

Additional publications by Dr. Sachs and colleagues showed the role of these ion channels in pathology for diseases like vascular disease, cardiac arrhythmias, muscular dystrophy, sickle cell anemia and cancer. Scientists soon realized that disease in any form can change the way tissues and cells respond to stretch and pressure in a variety of ways — through pressure from a growing tumor pressing on the surrounding healthy tissue; through a heart arrhythmia that causes the heart muscle to contract with unsynchronized force; or through long-term stiffening of arteries that are under prolonged increased blood pressure from stress.

For many years these channels were being studied in normal physiology and disease using Dr. Sachs’ technique, but without knowing the identity of the protein that actually provided the ability to respond to stretch and pressure.

It wasn’t until Dr. Patapoutian discovered the amino acid sequence of these channels that we knew their identity. And this discovery allowed researchers to investigate how expression of the channels in different tissues changes during normal development and their abnormal function contributes to disease. It also allowed more detailed studies of how the channels respond to stretch forces in different environments.

The role of these channels in disease led Dr. Sachs to search for blockers as a way to ameliorate negative effects of the overactivity of these channels.

Dr. Sachs teamed with me and Dr. Philip Gottlieb, also researchers in the Department of Physiology and Biophysics, to search for compounds that could block the channels. We hunted for compounds in spider and scorpion venom, and discovered an effective blocker of Piezo channels in the venom of the Chilean Rose tarantula and called it GsMTx4.

We then discovered the compound’s unusual method of blocking, which so far has proven difficult to duplicate. To improve the lives of patients suffering from disease, we launched a biomedical company called Tonus Therapeutics to develop this blocker, which is now made as a synthetic version of the original tarantula venom compound.

The Sachs/Suchyna/Gottlieb lab continues to study pressure/touch sensitivity here at UB. We use a variety of novel techniques to provide new insights into the role of Piezo channels in living systems and into the development of therapeutic strategies to treat disease. The recognition of the Nobel award committee to pressure/touch sensitivity as a milestone in biology and medicine will bring welcomed exposure to the field for funding and help to attract young scientists into this important area of research.