Interview by Morena Citriniti and Giulia Da Re with our excellent microscopic technician Patrizia Sabatelli from the Institute of Molecular Genetics of the CNR of Bologna.
Patrizia, we, the veterans of the Collagen sixth group, have known you for many years. We have always seen you in action during what we consider “the most crucial” times of biopsies, which are also indispensable for understanding the outcomes of the clinical trials/experiments conducted so far…
You have seen the group of patients and families grow into a real association and you are always involved with your smile and positive energy. It’s time to get to know you better.
Tell us, firstly, about your academic and educational background.
My education began at the University of Siena in the early ’80s, where I attended a course for Technicians of Medical Biological Institutes, and I fell deeply in love with the transmission electron microscope, which at that time was the most sophisticated instrument for the study of neuromuscular diseases. I was immediately recruited as a technician at the Laboratory of Neuropathology of the Institute of Neurological Sciences of Siena, and I had the opportunity to spend some years at the Institut de Myologie in Paris, directed at that time by Professor Michel Fardeau, specialized in the diagnosis of muscular dystrophies, and the Institute of Neurological Sciences of the University of Verona, directed at that time by Professor Nicolò Rizzuto, where I learned diagnostic techniques and the basics for interpreting alterations. From Siena, I moved to Bologna to the Institute of Molecular Genetics of the CNR (IGM-CNR), at the Rizzoli Orthopedic Institute, where I have been working for 35 years. There I had another stroke of luck, I met Dr. Luciano Merlini, with whom I immediately started collaborating on neuromuscular diseases.
How did you come to study Collagen VI? And what motivates you to stay in this field?
How did I get there? A series of fortunate coincidences: in the late ’90s, Dr. Luciano Merlini had described some families affected by Bethlem myopathy in which they had identified collagen VI as a possible responsible protein, and simultaneously, at a Telethon conference, I met Prof. Paolo Bonaldo of the University of Padua, who had just discovered that his murine model (which does not express the alpha 1 chain of collagen VI) was unexpectedly myopathic. I thus had the opportunity to study the tissues of the knockout mouse (i.e., mouse affected by collagenopathy), and the muscle biopsies of the patients, and I realized that there were common alterations at the mitochondrial level. From there, the story you probably already know. Why am I so stubborn on the topic? There is still so much to discover, it is a complex protein with different functional aspects, moreover tissue-specific.
What are you currently working on at the CNR Laboratory?
At the moment, I am involved in some research projects in collaboration with Prof. Paolo Bonaldo of the University of Padua and with Prof. Cesare Faldini, orthopedic surgeon, head of the Clinic I of the Rizzoli Orthopedic Institute of Bologna. The main focus is the study of tendon and muscle fascia alterations associated with collagen VI deficiency. For about 15 years our attention has been focused on skeletal muscle, which is certainly the most affected tissue in this type of pathology.
However, muscle function also depends on the proper functioning of associated connective structures, such as the tendon and muscle fascia, where collagen VI is highly expressed. Patients affected by collagen VI myopathies also show contractures, which worsen motor ability. We think that a deeper understanding of the role of collagen VI in the tendon and fascia may provide further important information on the mechanisms, and possibly new insights for corrective interventions. In particular, in collaboration with Dr. Vittoria Cenni of the IGM-CNR, we are studying the role of collagen VI during mechanical stimulation, paying attention to a specialized sensor of the cell, the primary cilium.
In parallel, in collaboration with the Dermatological Clinic of the University of Bologna, I am carrying forward a study on the scalp, to delve into the causes of alopecia areata associated with collagen VI diseases. Here the road is definitely complicated, also because there is no literature on the subject. We are opening a breach, which could reserve some surprises.
What is the work you have completed or goal you have achieved to date that you are most proud/content/satisfied with?
Thanks to Dr. Merlini’s foresight, I understood that since these are rare diseases, even if laborious and costly, because it requires a lot of work and funding, “nothing should be missed.” No information, no patient biopsies have been lost in these 30 years of activity, and this has allowed us as research progressed with discoveries on animal models, to validate possible mechanisms and treatments on human cells.
Without this work, it would not have been possible to conduct clinical trials or talk about therapy. Obviously, the greatest support was from the patients, who believed and understood that the flow of research needs to be supported, and in some way anticipated. The development of a therapy has mandatory steps, and the archives of biological material are an invaluable resource.
Have you faced obstacles in this work that you are particularly satisfied with overcoming? Which ones?
Every time something new starts, there are challenges, certainly the most demanding, since it did not admit errors, was that of clinical trials, particularly the one with Cyclosporine A.
Are you open to collaborations with other teams and/or universities (both Italian and international)? With which would you like to collaborate?
I have always been open to collaborations, generally I prefer to evaluate according to the proposal and the moment.
How much time do you plan to dedicate to your current work and do you already know what your goals are for the future?
I would say I have always been full time. What goals? Attending to the commitments made today.
Is there anything in particular you would like to say about collagen 6 deficiency diseases or in general to patients with col6 deficiency and/or their families, including those who have recently joined the association or who do not know you?
Mine is a scientific viewpoint, unfortunately, I do not think I can give useful messages to families, except all my understanding and commitment.
Is there anything in particular you would like to say to our readers and supporters and sponsors who know nothing about neuromuscular disease themes?
Unlike other muscular pathologies, where the defect is in muscle cell proteins (e.g., dystrophin in DMD), collagen VI is a protein of the extracellular matrix, in other words, of the environment in which the cells live. The presence of mutated col6 or its absence creates an “hostile environment,” in which probably the cells have communication problems, do not receive the correct stimuli, and maybe adapt in an incorrect way.
At the moment, it is not yet completely understood how this “hostile environment” impacts cellular function, and any initiative to elucidate the role of col6 should be encouraged. Therefore, basic studies need to be funded, there is still a long way to go. The difficulty is understanding how to restore a favorable environment, or how to restore the cellular functions themselves. Research is working in this sense.
As a microscopic technician of our medical scientific commission (I don’t know if you knew, but by accepting this interview you have consented to your nomination in the CMS of the col6 association) Do you want to say something about it? Suggestions etc.
Yes, I accept the nomination with pleasure.
You will come to the next gathering, right?
I will do everything to be there. A hug to both of you.
Thank you, you are a treasure.