"By combining bioengineering, imaging and stem cell modelling we will be able to establish advanced in vitro platforms to better understand the neurobiological mechanisms behind motor neurone diseases and dementias." Andrea Serio
UK DRI Group Leader
Andrea originally trained in Industrial Biotechnology at the University of Padova, and then moved to the San Raffaele University of Milan, where he studied Medical, Cellular & Molecular Biotechnologies for his Master's, which he obtained “summa cum laude” in 2008. In 2009 he was then awarded a scholarship to pursue his PhD at the University of Edinburgh, in the laboratory of Siddarthan Chandran. During this time, Andrea developed in vitro models of ALS based on cell populations derived from patient induced pluripotent stem cells (iPSCs). He spent several months in San Francisco, developing a collaboration with Steve Finkbeiner’s lab at the Gladstone Institute that allow him to develop an expertise in high content automated imaging. This was instrumental for his main project, which used iPSC-derived neurons and astrocytes to demonstrate glial cell-autonomus pathology in TDP43 proteinopathies for the first time. After obtaining his PhD in 2013, he moved to Imperial College London, to work with Molly Stevens at the Department of Bioengineering. There, Andrea developed a passion for biological engineering, helped by his original academic background, and worked on a number of projects that combined tissue engineering, neuroscience and biophotonics.
In 2017 he secured a Lectureship at King’s College London, where he established his independent laboratory focused on combining engineering, imaging and neuroscience. In 2019 he became a Group Leader at the Francis Crick Institute, where his lab was then seconded. There, he developed several novel strategies and technologies to model the nervous system in vitro using complex on-chip microfabricated devices and made important discoveries in the field of axonal biology. Finally, he was appointed as Group Leader within the UK DRI at King’s in 2023, where he applies his novel engineering neuroscience approach to uncover the mechanisms of degeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
1. At a glance
Cells are have been shaped by evolution to have a specific architecture. Some, like neurons have a long projection, the axon, which connects parts of the body that are sometimes metres away. Factors such as the length, size and shape of a cells can impact their biology in significant ways, and for neurons a significant part of the RNA biology and the molecular mechanisms that are involved in diseases such as MND and FTD happen away from the main cell body.
Dr Andrea Serio’s lab uses engineering, physics and neurobiology to investigate the interplay between the shape and structure of a cell and its function. In doing so, they hope to better understand the processes in MND/ALS that lead to the death of neurons.
2. Scientific goals
Dr Andrea Serio’s lab aims to investigate local RNA processing, temporal and spatial dynamics of RNA binding proteins (RBPs) in axons and dendrites, and generally the role that local RNA dynamics plays in neuronal function and dysfunction. The main area of work will be local RNA processing and RNA regulation in axons and dendrites, their interplay with other metabolic pathways and role in early molecular pathology of ALS/FTD molecular pathology. They aim to identify usable targets to modulate downstream toxic events that leads to early stages of cellular toxicity.
Main objectives and research goals:
- Applying tools to understand the effect of axonal length on RBP localisation and local RNA translation in ALS patient derived motor neurons, using a combination of transcriptomic analysis and super resolution imaging (supported by a Motor Neuron Disease Association Biomedical Research Project grant)
- Discovering the molecular signalling behind the length-dependent axonal regulatory mechanisms and their effect on local translation in axons (supported by a BBSRC Responsive Mode grant).
- Developing a high-throughput version of the axonal platform that will allow to perform correlative live imaging and complex transcriptomic studies to specifically study the mechanisms of RNA compartmentalisation in different part of the axon and the effect of different RBP mutations on the axonal RNA component, in collaboration with Prof. Jernej Ule at the DRI/Francis Crick Institute.
- Extending studies to cross-species comparison, to understand how basic aspects of axonal metabolic and translational regulation are orchestrated within different model organisms relevant for ALS research (mouse, rat and zebrafish)
3. Team members
Dr Cathleen Hagemann (Postdoc)
Dr Taylor Minckley (Postdoc)
Dr Eugenia Carraro (Postdoc)
Dr Sudeep Joshi (Postdoc)
Moreno Gonzalez (PhD student)
Pacharaporn Suklai (PhD Student)
Kelly O’Toole (PhD Student)
Ludovica Guetta (PhD Student)
Sofia Fredin (PhD Student)
Magnus Jhaveri (PhD Student)
Sofia Fredin (PhD Student)
Edward Jhaveri (PhD Student)
4. Collaborations
Within UK DRI:
- Prof Gipi Schiavo, UK DRI at UCL
- Prof Jernej Ule, UK DRI at KCL
- Dr Marc-David Ruepp, UK DRI at KCL
- Dr Edward Avezov, UK DRI at Cambridge
Beyond UK DRI:
- Francesco Saverio Tedesco, UCL
- Rickie Patani, UCL
- Mike Devine, The Francis Crick Institute
- Simon Ameer-Beg, KCL
- Mads Bergholdt, KCL
- David Lyons, University of Edinburgh
5. Topics
Bioengineering, In vitro Modelling, Neural Circuits, Axonal Biology, Stem Cell Modelling, Imaging technologies, 3D bioprinting, Tissue Engineering, Neurodegeneration
6. Techniques
3D printing, microfabrication, live imaging, microfluidics, organoid generation, transcriptomics, tissue bioprinting, high content imaging, in vitro screening
7. Key publications
CC Hsu et al. “Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates” ACS Applied Materials & Interfaces (2022) 14 (29), 32773-32787 (*co-first author )
Jiang, Y. et al. “Bioengineering human skeletal muscle models: Recent advances, current challenges and future perspectives” Experimental Cell Research (2022) (https://doi.org/10.1016/j.yexcr.2022.113133).
Hagemann, C. et al. “SOLID: Soft-lithography on SLA 3D printed moulds for fast, versatile, and accessible high-resolution fabrication of customised multiscale cell culture devices with complex designs” Biorxiv (https://doi.org/10.1101/2022.02.22.481424) (*Senior author )
Hagemann C. et al. “Axonal length determines distinct homeostatic phenotypes in human iPSC derived motor neurons on a bioengineered platform” Advanced Healthcare Materials (2022) 11 (10), 2270047 (https://doi.org/10.1002/adhm.202101817) . (*Senior author )
Bennet A. et al. “Comparative structural, biophysical, and receptor binding study of true type and wild type AAV2” Journal of Structural Biology Volume 213, Issue 4 (https://doi.org/10.1016/j.jsb.2021.107795)
“TDP-43 and FUS mislocalization in VCP mutant motor neurons is reversed by pharmacological inhibition of the VCP D2 ATPase domain” Brain (2020) 143 (12), e103-e103
Harley J, Hagemann C., Serio A*., Patani R*. “FUS is lost from nuclei and gained in neurites of motor neurons in a human stem cell model of VCP-related ALS” Brain (2020) (doi:10.1093/brain/awaa339)
