Dr Arno Alpi

Senior Lecturer in Molecular Genetics

Contact details

Address

Street

Institute of Cell Biology
Roger Land Building, G20
Alex Crum Brown Road

City
Edinburgh
Post code
EH9 3FF

Biography

Background

2024 -                Senior Lecturer, Institute of Cell Biology, University of Edinburgh, Edinburgh, Scotland, UK

2016 - 2024     Group Leader, Dept. of Molecular Machines & Signaling, MPI of Biochemistry, Martinsried, Germany

2009 - 2016     Group Leader, Scottish Institute for Cell Signaling & MRC-PPU, University of Dundee, Dundee, UK

2004 - 2009     MRC Career Track Fellow, Protein and Nucleic Acid Department, MRC Laboratory for Molecular Biology, Cambridge, UK

2004                   PhD, LMU Munich, Germany

2000 - 2004     PhD thesis, Department of Cell Biology, MPI of Biochemistry, Martinsried, Germany

2000                   Master/Diploma in Chemistry/Biochemistry, University of Vienna

1991 - 1999     Chemistry/Biochemistry, University of Vienna, Vienna, Austria

Research summary

  • Red blood cell development
  • Ubiquitin system
  • Proteostasis

Cell signalling pathways are essential for every organism to maintain cell homeostasis, cell behaviour, and to adjust cellular physiology in response to internal cues and external stimuli. Our major scientific focus is to understand signalling pathways that are controlled by ubiquitylation – a protein modification utilizing the small protein “ubiquitin” – which is known to impact the protein’s fate, such as its turnover and stability, subcellular location, assembly, conformation and activity. We combine proteomics, biochemistry, and cell biology to functionally dissect these ubiquitin signalling pathways and their molecular machines to understand their physiology and how their deregulation promotes cellular transformation and disease.

Current research interests

Human red blood cell development (erythropoiesis) is a multistep process that maintains stable erythroid homeostasis throughout life and replenishes more than 200 billion erythrocytes lost by senescence in healthy humans. Erythropoiesis is one of the most striking examples of developmentally programmed protein remodelling in the cell. Throughout this process, many erythrocyte-specific proteins are initially expressed, but then all cellular organelles and the majority of proteins are eventually eliminated in a stepwise fashion. These remarkable events are ultimately responsible for forming the proteome of mature erythrocytes. By measuring the proteomic landscape of in vitro human erythropoiesis models at various stages of differentiation, we found dynamic changes in the expression of components of the ubiquitin system – most strikingly for subunits of the >1.3 MDa CTLH E3 ubiquitin ligase complex (Karayel et al., 2020). We could further show that distinct CTLH E3 assemblies have important regulator functions in balancing dormancy of erythroid progenitors and their terminal differentiation into enucleated mature erythrocytes (Sherpa et al., 2022). To determine the mechanism of CTLH E3 function, we identified several CTLH E3-specific protein targets including metabolic enzymes. Current studies using in vitro cell culture systems to reconstitute erythropoiesis (including “erythroblastic islands” composed of central macrophages, which act as “nursing” cells, and erythroid progenitor cells) aim to dissect CTLH E3 function in metabolic rewiring during erythroid differentiation, as well as changes in the epigenetic chromatin landscape.
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