Penney Gilbert leads international team to study how physical stress turns on genes in stem cells

Professor Penney Gilbert

IBBME professor and Donnelly Centre principal investigator Penney Gilbert partners with researchers from Germany and the U.S. to study how physical stress triggers the expression of genes in muscle stem cells, which may provide new insights into human disease. (Photo: Luke Ng / University of Toronto)

March 27, 2017 | By Tyler Irving and Luke Ng

Can you activate a stem cell by squeezing it? A new international collaboration led by Professor Penney Gilbert aims to find out.

The researchers will study how muscle stem cells turn genes on and off in response to physical stresses that arise in response to tissue injury. Their results could lead to new treatments for genetic diseases.

“Every cell in the human body has the exact same genetic material, but our hair cells look and act very differently than the cardiac cells that pump our heart because of the way different genes are turned on in distinct cell types,” says Gilbert.

However, when the process of turning genes on or off fails, disease often ensues.

While scientists have already uncovered many of the secrets that explain how and when genes are turned on and off, most of them involve ‘chemical cascades’ of signaling molecules and cell receptors. Much like a Rube Goldberg Machine, where an initiating event triggers an elaborate series of subsequent actions, these methods can take a long time to achieve the final result.

Gilbert and her colleagues believe that faster methods exist. For example, under certain circumstances, physical forces — as opposed to chemical changes — could cause certain genes to become activated or deactivated.

“Muscle stem cells are sprinkled within skeletal muscle tissue, and these tiny cells are first responders when this tissue becomes injured,” says Gilbert. “To do their job they transition from having very few genes turned on to all of a sudden turning on lots of genes all at once.” The team suspects that the trigger for this transition may be the shear, compressive and tensile stresses experienced as a result of injury to the muscle.

Gilbert muscle stem cell research Rube Goldberg Machine analogy

Much like a Rube Goldberg Machine, genes can turn on and off as a result of a series of chemical cascades downstream of an initiating event (Path 2). HFSP funding will explore whether physical forces can more directly influence gene expression (Path 1). (Image: Maria Abou Chakra).

The new partnership is funded by a $1.4 million grant from the Human Frontier Science Program (HFSP). It brings together Gilbert’s expertise in muscle stem cells with advanced methods in biophysics from Professor Timo Betz at the University of Münster, as well as molecular imaging techniques developed by Professor Xavier Darzacq at the University of California, Berkeley. Together the team will comprehensively examine the ways in which muscle stem cells transmit the physical stresses they experience into changes in their DNA and gene expression.

The results of the study could provide scientists with new, non-chemical strategies for turning genes on and off, not only in muscle stem cells, but other cell types as well. This in turn could help treat genetic diseases or other conditions caused when genes fail to turn on or off in the right place or the right time.

“To nail down our idea we must work together since we each bring a different expertise to the table,” adds Gilbert. “We are so grateful to HFSP for fundamental research support—they allow scientists the freedom to follow their creativity.”