2022: Antje Rottner
Dr Antje Rottner completed her DPhil under the supervision of Professor Anna Gloyn at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) aiming to identify genes that influence Type 2 Diabetes risk through human pancreatic beta cell dysfunction.
Since listening to her first undergraduate lecture on genetics at the University of Erlangen-Nuremberg in Germany, Dr Rottner has been fascinated by the possibilities of genome editing and how the insights gained from genetic studies can be applied to better understand the underlying disease mechanisms, leading to targeted and improved therapies.
She followed her interest to the UK to obtain an MSc in Cell and Gene Therapy at University College London (Scientific Reports, 2022) before securing an RDM scholarship to pursue a DPhil in Professor Anna Gloyn’s group at OCDEM.
Dr Rottner’s DPhil research focused on using genome editing to advance the understanding of genes and mechanisms involved in Type 2 Diabetes risk and pancreatic beta cell dysfunction. To simultaneously investigate the impact of thousands of genes, she performed the first ever genome-wide CRISPR screen in human pancreatic beta cells, thus generating the first unbiased and genome-wide functional knockout dataset for human beta cell function and causal Type 2 Diabetes genes (in press, Nature Genetics 2022).
One of the screening hits, the autophagy receptor CALCOCO2, was particularly interesting, as it had been previously associated with Type 2 Diabetes in genetic studies; however, its underlying functional mechanism was then unknown. Further follow-up by Dr Rottner and her colleagues showed that loss of CALCOCO2 in human beta cells induces abnormal mitochondrial structure and autophagy, as well as a reduced number of insulin-precursor-containing granules. Dr Rottner’s CRISPR screen has therefore significantly contributed to our understanding of human pancreatic beta cell function and identified many promising causal candidate gene for Type 2 Diabetes, laying the foundation for many future studies.
As part of her DPhil, Dr Rottner also developed a novel pipeline to generate CRISPR edited cells in an authentic but highly challenging human beta cell model, which has been fundamental in obtaining insights into the role of genes involved in Type 2 Diabetes such as PAM and RREB1 (Wellcome Open Research 2020, Nature Genetics 2019, bioRxiv 2022).
Dr Rottner was also the recipient of a prestigious Albert Renold Travel Fellowship from the European Association for the study of Diabetes (EASD), which funded a three-month research stay at Stanford University to work with collaborators on confirming her findings on CALCOCO2 in pancreatic primary human islets. She has further been recognised with the Early Career Professional Impact Award (ECP) by the European Laboratory Research and Innovation Group UK (ELRIG) in recognition of the outstanding scientific work performed in her DPhil as well as her efforts beyond the lab.
Dr Rottner says that she has greatly benefited from the collaborative and supportive environment within OCDEM and RDM. She is immensely grateful for all the support she received throughout her DPhil and to everyone who made this project not just a success but also a joy to work on. She has further been actively involved in setting up cross-departmental public engagement activities such as the DNA Origami exhibition for the Royal Society Summer Exhibition, the Cheltenham Science festival and multiple workshops at Headington School, Oxford.
Since completing her DPhil, Dr Rottner has taken up a position as Postdoctoral Fellow at AstraZeneca in Gothenburg, Sweden to build on her interest in using genome editing to understand the molecular mechanisms underlying disease causing mutations.