Early Stage Investigator Award for Alec Smith

Alec Smith (L), an Instructor in the Department of Physiology and Biophysics, has received a Young Investigator grant to support his independent muscle research.

When Alec Smith arrived at the University of Washington in 2014, the postdoc from London brought bona fides in disease modeling, a keen interest in neuromuscular research, and a desire to establish himself as an independent researcher in a collaborative environment.

Landing in a lab affiliated with the Institute for Stem Cell and Regenerative Medicine (ISCRM), Alec soon found the mentors who would support his growth and ample opportunities to build on his experience by mastering the art of differentiating stem cells into neuronal and skeletal muscle.

Six years later, Alec is now an Instructor in the Department of Physiology and Biophysics, and the muscle research community he joined is growing and galvanizing, buoyed in just the last twelve months by two major grants. One grant gave rise to the Center for Translational Muscle Research at UW Medicine, which began operating in the spring of 2019. The other grant, from the National Institute of General Medical Science (NIGMS), is funding a partnership between the University of Washington, Stanford University, the University of California Santa Barbara, and the Curie Institute in Paris.

Muscle Center Diagram
Pilot awards supporting young scientists are just one aspect of the UW Medicine Center for Translational Muscle Research

ISCRM faculty member Dr. Mike Regnier is a Professor Bioengineering, the Director of the CTMR, and the lead UW researcher on the NIGMS grant.  “The CTMR and the NIGMS grant are two ways we are expanding muscle research here at UW and at the same time creating pilot grant programs that provide critical early-stage funding for young scientists like Alec who are making the leap from postdoc to independent researchers.”

For Alec, both grants represent career boosts. The CTMR offers access to expertise, instrumentation, computation, and other resources designed to increase the pace and precision of muscle research for early investigators and senior scientists alike. The NIGMS grant put Alec in the middle of an international collaboration focused on muscle mutations at the molecular level. Now an early stage investigator award, funded by the parent NIGMS program, has provided two years of funding to support his own independent research.

Early Stage Funding Propels a Young Scientist

Money matters at every career stage of course, but Early Stage Investigators like Alec are faced with a particular challenge.  “It’s a catch-22,” he says. “To get exciting data, you need funding. But getting the funding requires demonstrating that you already have working protocols and technologies; and that requires data. So, two years of funding for my own project is huge. It will not only allow me to study a fascinating area of muscle biology, but will also set me up to apply for future grants to continue my career.”

ISCRM faculty member David Mack, PhD with graduate student Samantha Bremner

This path-to-independence grant has broader benefits says ISCRM faculty member Dr. David Mack, Associate Professor of Rehabilitation Medicine and co-investigator on the NIGMS program.  “Supporting talented young scientists ensures that ISCRM will thrive for years to come,” says Mack. “Alec has now proven his ability to bring in money, which is typically the last hurdle to independence.  But equally important to our team, he embodies the spirit of academic camaraderie and his skills allow us to investigate new aspects of muscle biology that we couldn’t before he joined.  That’s why we invest in young scientists.”

With the money comes stability – and affirmation.  “To put something out there as an original idea and have that supported by titans in the field is very exciting.”

Studying Cells Muscle Cells in 3D Structures

Specifically, Alec has received funds as an Early Stage Investigator to use 3D models and stem cell-derived tissues to better understand how mutations in a protein known as myosin heavy chain 3 impact skeletal muscle development.  Alec expects studying human cells in a 3D structure that closely recreates a cell’s natural environment will yield much more information than investigations based on two-dimensional cell culture studies.

Throughout the body, myosin is a critical part of the machinery that makes it possible for muscles to contract. The multi-institutional research team funded by the NIGMS grant is combining areas of expertise in biophysics, bioengineering, chemical engineering, cardiology, computational modeling, embryology, and stem cell biology to study how serious skeletal muscle and heart problems originate with tiny alterations in myosin structure.

Alec is particularly interested in the relationship between mutations in myosin heavy chain 3, which in humans appears only for a period of time during the development of the embryo, and muscle disorders that might appear in the womb or later in life.  The X-factor in Alec’s approach is a 3D model that allows the researchers to observe how cells contract just as they might in a human body.

The idea of using 3D models to measure the force of muscle contractions originated more than twenty years ago when researchers began suspending cells between posts that were engineered to respond to tiny movements. However, Alec is introducing a twist. Adapting technology developed by ISCRM faculty member Dr. Nate Sniadecki, Professor of Mechanical Engineering, Alec’s model will use magnets to calculate the force required to generate the movement of similar posts, only in a much more rapid, automated fashion.

Two Post Technology and a Path to Potential Therapeutics

Skeletal muscle 3D tissue stained for desmin (green), alpha actinin (red), and nuclei (blue).

“This grant is an opportunity to marry established two-post technology with magnetic sensing to look at multiple tissues under multiple conditions simultaneously,” explains Alec. That’s very important for myosin heavy chain 3 studies because there’s only a short amount of time during development when the protein is actually expressed and potentially causing defects. We need to be sure we are capturing that window, so non-invasive monitoring will allow us to better define the period when the mutant protein is active. Add to that the stem cell models from the Regnier and Mack labs and everything is coming together at the right time.”

While Alec is innately motivated to understand why things happen, he’s aware his research could have important implications for human medicine.  “Down the road, the development of a three-dimensional skeletal muscle tissue model would be incredibly valuable for testing new therapeutics in human cells as opposed to animal models.”

For now, Alec is quick to stress the importance of the ISCRM environment to his research.  “I would not have the opportunity to pursue a project like this or attempt the transition to greater independence without the support of my mentors and the ISCRM community. To me, the collaborative nature of ISCRM is just a better way of doing science.