About me
I graduated with a First class undergraduate degree in Biology from the University of Manchester in 2023, where my course choices were focused in the fields of molecular and cell biology, and biotechnology. During my degree, I became fascinated by the prospect of engineering of biological systems to manufacture high yields of complex therapeutics, from mammalian cell line engineering for recombinant protein production, to the engineering of molecular components for the synthesis of oligonucleotides. At UoM, I was selected to participate in an International Exchange Programme, which allowed me to study for a semester at the University of Toronto, where I was part of the Molecular Genetics Department, in the Temerty Faculty of Medicine, and I had the opportunity to learn more about molecular genetics analysis, modern biotechnology techniques and developmental genetics.
In the summer between my second and third year, I undertook a placement at AstraZeneca within the BioPharmaceutical Development department, working in Upstream and Downstream Bioprocessing for the Live Attenuated Influenza Vaccine (LAIV) “Fluenz Tetra”. This placement was instrumental in my choice of field of study, as I witnessed the direct impact that research, development and optimisation work has on a product that is then rolled out to the public. I not only decided I wanted to pursue research in biopharmaceutical therapeutics and bioprocessing, I also realised I enjoyed working in collaboration with industry to be able to bring discoveries to patients.
During my final year of university, I was lucky to experience biopharmaceutical research in Prof Alan Dickson’s lab in the Manchester Institute of Biotechnology, within the Centre of Excellence in Biopharmaceuticals (COEBP), where I helped out on a CHO secretory pathway engineering project. Alongside this, I completed my final year project in Dr Kathryn Hentges’ lab, studying the subcellular localisation of mutant Slit3 and its implication in Tetralogy of Fallot, which fuelled my other big passion for the genetics of human disease.
Last summer, I also completed an internship within the R&D department within the Clinical Services function of Illumina. My role within Assay Development for Whole Genome Sequencing was to optimise a manual library prep protocol to prepare samples for sequencing with NovaSeq6000. This placement gave me the chance to learn more about genomics and the critical role of next-generation sequencing in both patient diagnosis and care and the drug development pipeline. I am very happy to start my PhD journey at The University of Sheffield in Dr Adam Brown’s lab, in a very active lab group with many industrial collaborations. Plus, I am happy to be working with AstraZeneca again! I greatly enjoy working at the intersection of industry and academia, as I believe great results can come out of these collaborations. I also enjoy science outreach, and have been involved in a variety of outreach events such as British Science Week at the Manchester Museum and Science Alive here at the University of Sheffield.
Outside of the lab, I really love playing sports, especially running, skiing and playing (and coaching) basketball.
My Project
The remarkably rapid development, clinical testing and deployment of mRNA vaccines against SARS-CoV-2 was instrumental in altering the course of the Covid-19 pandemic, effectively preventing millions of deaths globally. The significant impact of mRNA vaccines, coupled with the safety profile now validated by billions of administered doses across the world, highlight the true potential of mRNA technologies as a revolutionary tool not only for pandemic response, but for novel, complex therapeutics able to treat “undruggable” targets.
Synthetic mRNA has the potential to encode a large range of protein types, which makes it suitable for applications such as cancer immunotherapy, protein replacement therapy, genome engineering and genetic reprogramming. mRNA is manufactured through a cell-free process called In Vitro Transcription (IVT), the core components of which are a phage single-subunit DNA-directed RNA Polymerase and a linearised DNA template displaying a suitable promoter for the polymerase of choice.
However, little is known on the mechanistic interactions of polymerases with their promoters, and their impact on yield and quality profile of mRNA products. This is particularly true when considering next-generation mRNA therapeutics, which are longer and more complex, posing a significant manufacturing challenge if using standard IVT components. Because of the potential of these novel therapeutics to improve patient outcomes, it is essential to develop and optimise tools for the manufacturing of these molecules at increased yield and quality.
In this collaborative project, we will investigate the impact of polymerase-promoter pairs in IVT production of long, complex, next-generation mRNA therapeutics. We aim to develop a platform with an engineered promoter-polymerase pair that is optimised specifically for its ability to manufacture these next-generation mRNAs using synthetic biology techniques such as high throughput screening, directed evolution of proteins, as well as computational approaches. The collaboration with AstraZeneca is a perfect opportunity to work alongside industry experts and understand the commercial impact of our research.
Connect
Twitter: https://twitter.com/Alessandra_Sbtn
LinkedIn: https://www.linkedin.com/in/alessandrasabatini-as/