“esprit de corps” by Matthias Hebrok, PhD

For the last 20 years I have been getting up early in the morning, have a coffee, and then drive myself to the Diabetes Center at the University of California, San Francisco (UCSF), where I direct a research group focusing on beta cell biology.  In addition to overseeing a thriving research laboratory I am also serving as the Director of the Diabetes Center.  The goal of our efforts in the Center is to develop cures for diabetes.  As of today, I have not set foot in my laboratory at my institution for the last 7 weeks.

As for many of us, my transition from ‘going to work’ to ‘working from home’ was abrupt and came with little warning.  The COVID-19 epidemic that arrived at our doorsteps this spring has thrown all of our lives in turmoil, uprooting our normal routines and affecting almost all aspects of our daily activities.  The disease also has changed the way we can and are conducting biological research in our laboratories at UCSF and around the country. 

Before COVID-19 the majority of the 120+ members of the Diabetes Center were involved in designing, executing, and analyzing experiments in the areas of immunology, beta and stem cell biology, and obesity/nutrition.  Members of my laboratory would work long hours on testing novel hypothesis to find new ways how to manipulate stem cells and turn them into pancreatic beta cells that can produce and secrete insulin under physiological conditions.  Our work was challenging, but also exciting as we were at the forefront of stem cell science using cutting edge technologies to manipulate the genetic code of stem cell derived beta cells and study the outcome.  Setting up our stem cell technology took more than a decade of hard work and the journey was marked by lots of surprises, excitement, and sometimes temporary despair when things just did not work out the way we expected and we had to go back to the ‘drawing board’ to come up with a different strategy.  While appreciating the peaks and persevering through the valleys, we made steady progress and succeeded in generating functional insulin-producing beta cells from stem cells that were in most aspects comparable to the cells we have in our own pancreas.  Being able to generate such cells, and to genetically modify them at will, for example eliminating or replacing just one of our 3 billion base pairs that make up the DNA of each of our cells in our body, opened up possibilities to understand and shape aspects of beta cells in a manner that was unprecedented.  We have taken full advantage of this technology and were about to complete a number of promising projects in which we defined the activities of a novel regulator of beta cell metabolism, identified a new way how beta cells maintain their functional properties, and changed the expression of molecules that the immune system uses to identify and target cells upon transplantation.  Then the virus arrived and we had to adjust to the new reality.

Scientists working with stem cells need to be physically present in their laboratories to generate their data.  Scientific exploration starts with a hypothesis often based on prior work.  Experiments are being designed and then executed to validate or falsify the premise.  Data are being collected using a variety of sophisticated assays.  In my laboratory we probe specific functions of beta cells, for example the amount of insulin being secreted upon stimulation with a glucose challenge, the hallmark activity of an insulin-producing cell.  All of this work depends on scientists, often working in teams, being able to have access to our laboratory facilities and our sophisticated instruments.  Most, if not all of these activities are currently on hold due to the mandatory COVID-19 shutdown.

In addition to causing a delay in data generation, the current situation puts undue stress on many members of our community, from graduate students who need to complete their thesis to postdoctoral fellows being concerned about publishing their findings in time and securing a position in academia or industry.  Principal Investigators worry about whether these delays might affect funding for their laboratories in the future.  So far funding organizations have been supportive and great partners during the shutdown

My colleagues and I are making the best of the imposed lockdown.  We virtually connect with our lab members and friends to discuss how we consolidate our data into scientific publications, develop new hypothesis to test when we go back to work, and reevaluate the focus and direction of our laboratories.  There is a tangible ‘esprit de corps’ in our community and a clear feeling that we will make it through these trying times.  If we have learned something from COVID-19 it is the need for accurate data obtained via scientific exploration to guide our efforts and approaches.  Academic institutions are at the forefront of the discovery efforts and essential in our quest to combat diseases, including COVID-19 and diabetes.  I am hopeful we will emerge reinvigorated from this crisis with continued support from our T1D community.

How are we going to restart our work?  We are in unchartered territory, but the safety and well-being of our laboratory members and staff are of utmost importance.  Many of our states are lifting the restrictions and we are developing plans to re-start our work as well.  We likely will do so in phases, initially allowing just a small number of scientists back to work to ensure we are not infecting our staff and eventually ramping up our efforts.  It will take time to get back to what we considered ‘normal’ mere 2 months ago, but we are getting ready to do so. 

I am thankful of the outpouring of support my colleagues and I have received from our wider community.  We are eager to resume our work and are looking forward to reconnecting with you on our common journey.  With your help, we will make it back stronger and continue our efforts to cure diabetes.