PhD FELLOW # 6

DIEGO CAPELLI

WP2: NOVEL STRATEGIES FOR COUPLING & IMMOBILIZATION

STABILIZATION OF GROWTH FACTORS WITH NON-CANONICAL AMINO ACIDS

Biography

I am a researcher in the field of biotechnology and pharmacology, with a solid and diverse academic background. I obtained my Bachelor’s degree in Biotechnology at the University of Milan Bicocca, where I deepened my knowledge in the field of molecular biology and laboratory techniques. Subsequently, I continued my studies at the State University of Milan, obtaining a Master’s degree in Pharmacology. During my training, I showed a strong interest in scientific research, focusing on my master’s thesis on the development of therapies for mental illnesses. For this project, I had the opportunity to work at the ZI Research Centre in Mannheim, Germany, conducting in vivo studies on animal models and in vitro studies at the Pharmacological and Molecular Sciences research laboratory of the University of Milan. Furthermore, I enriched my academic experience with a six-month research period at a laboratory specialized in molecular dynamics in silico, also at the University of Milan. This experience allowed me to acquire advanced skills in the computational analysis of biological processes.

Tell us a bit about your PhD project

Fibroblast Growth Factors (FGFs) are a family of proteins that regulate numerous mechanisms within complex organisms, including cell migration, proliferation, differentiation, and survival. Consequently, there is a growing interest in both academia and medicine to exploit them for various purposes such as wound healing, cancer treatment, and bone tissue repair. In this PhD project, we address the incorporation of amino acids that are not part of the human genome, known as non-canonical amino acids (nc-aa). The emergence of robust methods to expand the genetic code makes it possible to incorporate nc-aa into the polypeptide chain of proteins, thereby improving their stability and activity by introducing new functionalities and chemical properties into enzymes. In this project two state-of-the-art methods will be used: Selective Pressure Incorporation (SPI) and Stop Codon Suppression (SCS). With SPI, we will globally replace natural aa with the corresponding non-canonical counterparts through residue-specific incorporation to evaluate the effect of modifications on FGF protein stability and to understand the general applicability of nc-aa incorporation to improve FGF proteins. With SCS, we will use site-specific incorporation to introduce nc-aa at a specific position that will act as a handle with click reactions for immobilization or interaction with other biological entities.

Tell us about your research interests – what do you expect from the consortium

My main research interests revolve around the design and optimisation of biomolecular therapies for complex diseases such as cancer and severe injuries. I strongly believe that proteins can play a key role in this context, given their ability to regulate key cellular processes such as proliferation and differentiation. My current PhD project offers me the unique opportunity to explore the use of nc-aa to improve FGFs properties such as stability and activity. I am convinced that this innovative approach can lead to the creation of more effective and safer therapies, reducing the side effects often associated with conventional treatments. In the context of the consortium in which I work, I expect to actively collaborate with highly qualified colleagues from different scientific disciplines. Thanks to the secondments, I will have the opportunity to experience unique cultural exchange and to share knowledge and discoveries with other team members. I am confident that this multidisciplinary cooperation will enrich my research career and allow me to contribute significantly to the success of our projects. In conclusion, I am excited to continue exploring new avenues in biomedical research and to contribute to the advancement of molecular medicine. I am grateful for the opportunity to work within a dynamic and collaborative consortium and look forward to embarking on this exciting scientific adventure together with the team.

Hobbies

Cooking, play football, and driving my motorbike

Favorite TV series

Breaking bad

Favorite city 

Genova

at what Harry Potter house do you belong?

Gryffindor 🦁

PyMOL or Chimera?

Chimera 🙂

Organization

Enantis , Czech Republic

Doctoral Supervisor

Dr. Jan Vilim

Enrolment in Doctoral degree

Masaryk University (MU)

Secondments

At University of Manitoba (Winnipeg, Canada) with Prof. Nediljko Budisa & The Center for Cooperative Research in Biomaterials (San Sebastian, Spain) with Dr.Fernando López-Gallego

Objectives

• Rational design of selected growth factors as therapeutically- and biotechnologically-attractive proteins using incorporation of non-canonical amino acids (NCAA)
• Production and characterization of selected NCAA incorporating proteins 
• Development of a method of selective chemical modification of selected proteins and enzymes using incorporated NCAA
• Development of a method for site-specific immobilization of growth factors using NCAA

 

Fields related to the project

(1) Computational biology

(2) Protein engineering

(3) Biocatalysis