Michael Munson, PhD – Associate Principal Scientist Respiratory & Immunology, AstraZeneca
Michael Munson, PhD – Associate Principal Scientist Respiratory & Immunology, AstraZeneca
Biography
Michael Munson is an Associate Principal Scientist based at AstraZeneca, Gothenburg, Sweden working currently within Respiratory & Immunology. He is a cell biologist and imaging specialist whose research has been focused on intracellular trafficking, spanning autophagy, endocytosis and nanomedicine delivery. He completed his studies, followed by PhD at the University of Dundee, Scotland (in the group of Prof. Ian Ganley), where he began a career interest of cellular trafficking pathways combined with imaging. Initially focusing upon endocytosis and lysosomal trafficking pathways, he moved to mitochondrial autophagy (mitophagy) by taking a Postdoc position at the University of Oslo (in the group of Prof. Anne Simonsen). He then began a Postdoc followed by Senior Scientist position within AstraZeneca, Sweden in the Advanced Drug Delivery, Pharmaceutical Sciences department to work on characterising early stage mRNA-delivery vehicles formulation and efficacy.
Interview
NanoSphere: Tell us a bit about yourself—your background, journey, and what led you to where you are today.
Michael: I started out originally studying quite a broad biomedical science degree at the University of Dundee, but this quickly changed once I got exposed to some of the nitty gritty lectures on cellular signalling. I found this mechanistic understanding and explanation much more captivating than broader physiology. As such, I switched to a Biochemistry and Pharmacology degree that naturally felt more fitting for me. I then secured a PhD at the medical research council protein phosphorylation unit (MRC PPU) in Dundee and rotated in two labs before deciding where to spend my main PhD studies. This was eye opening and formative, as my second rotation was spent in the lab of a young and energetic PI (now Prof. Ian Ganley) who was just establishing his own lab. I was taken in by his enthusiasm for his research interests (autophagy) but also his approaches (microscopy) that started my own career that has since appreciated and relied heavily upon microscopy as a readout. Whilst my microscopy interest grew, I became increasingly aware of limitations and potential for bias. This motivated me to start a journey on learning to apply automated image analysis to improve data robustness. After my PhD, I took a postdoctoral position in the lab of Prof. Anne Simonsen at the University of Oslo and implemented an imaging-based siRNA screen to identify novel regulators of mitochondrial degradation (mitophagy), scaling my experience from simple coverslides to working in 96-well plates. I had the opportunity to start applying more complicated imaging pipelines and analysis, and with the help of a great team we managed to validate the effect of several hits on mitophagy across organisms. By chance I saw an industrial postdoc position at AstraZeneca in Gothenburg under the supervision of Dr. Alan Sabirsh. The project focused upon intracellular trafficking of LNPs, and whilst I had no real understanding of what an LNP was at that stage (pre-COVID-19 pandemic), I did have experience in cellular trafficking and imaging that was ideally suited for this area. This was an excellent fit, especially given that Alan also runs the core imaging facility at AstraZeneca, Gothenburg, and thereby cultivated and supported an even greater appreciation of imaging readouts. Starting at AstraZeneca gave me access to a whole-new level of automation and liquid handling infrastructure that I never knew existed, and I was excited to utilise these, enabling me to continue my imaging journey towards working within 384- and 1536-well plate formats in a robust and unbiased manner. The ability to automate and scale is liberating. Instead of having to pick and limit what variables to look at experimentally, it opens the possibility to scan multiple variables in all directions, building a more complete overview of how formulation or experimental differences can adjust responses. This has been the basis of much of my research since, with most of my contributions leveraging in some manner the combined power of automation and microscopy to evaluate delivery vehicles, advancing our understanding of how formulation impacts function. Most recently I have switched to the Respiratory and Immunology department, and I am now learning more about the challenges in the respiratory space for diseases such as COPD.
NanoSphere: You’ve worked on both fundamental trafficking pathways (like autophagy and ESCRT regulation) and applied delivery systems (LNPs, dendrimers, engineered vesicles). Given that endosomal escape remains the ‘great wall’ of nanomedicine, what do you see as the most promising cellular pathways or mechanisms we should be targeting to finally improve cytosolic delivery at scale?
Michael: As you rightly highlight, endosomal escape is incredibly important for the efficacy of nanomedicines, and for a long time delivery vehicle design and research has been focusing on increasing this at whatever cost. It is dependent upon cellular uptake, making it hard to effectively delineate how chemistry and formulation alter these two stages of the delivery process. To date, a lot of progression has been made in improved cellular uptake, so that the limited % of material that is released is relatively larger. Reliable monitoring and quantification of endosomal escape is essential for understanding how our formulations perform before being able to proactively modulate it. When I started at AstraZeneca in 2018 there were various assays published in how to potentially quantify this1, but nobody had adapted this to a scalable and screenable format or tried to derive correlations between different stages of LNP-mRNA delivery as a consequence of formulation. One core aspect of my research in recent years has therefore been trying to apply imaging-based assays that can identify remodelled endosomes with reporter proteins, such as Galectins, enabling key stages of LNP-mediated mRNA-delivery (uptake, endosomal escape, translation) to be quantified independently of one another 2. Imaging assays such as this are very tractable for applying as higher-throughput screening approaches, and we have been applying this with a range of delivery technologies to help inform formulation design choices 3. We have also shared this tool with the community in the hope that this accessibility increases utilisation and progress, the tool Galectin-9 plasmid we use to quantify endosomal remodelling is available via Addgene and has been shared with >75 labs around the globe4. Beyond Galectin-9, we are interested in other endogenous markers of remodelling that play a role in the cellular response and resolution5. Endosomal escape has been simple to label as a single process, but within that definition it appears to take different forms, and the cellular response and resolution to that insult can differ. I believe this variance and nuance is starting to become much more appreciated, alongside the understanding that less can sometimes be more 6. As we delineate differing forms of endosomal remodelling, we have the chance to understand which approach is actually best tolerated and most feasible for delivery at scale. I don’t believe a single breakthrough will be sufficient, but rather a number of incremental advances that will gradually improve subversion of this cellular defense mechanism.
NanoSphere: Many young researchers get frustrated seeing brilliant mechanistic findings in cell biology stall before reaching patients. From your perspective, what do academics need to do differently — or what should industry enable better — so that discoveries in trafficking and delivery have a clearer path toward clinical nanomedicines?
Michael: I think there is a disconnect between making those brilliant discoveries and the layers of complexity that inevitably come into play as you scale to whole organisms and towards the clinic. In vitro experiments are very ‘clean’ and can greatly simplify systems down to individual cell types, which can be great for studying particular events in isolation and building understanding. However, the whole body is a complex environment with additional physical barriers and interplays between organs and cells that are difficult to model or predict. Translating in vitro to in vivo findings is notoriously difficult, no matter the drug modality. We have been applying in vitro screening coupled with design of experiment and machine learning approaches to try and understand what features are important for efficacy and demonstrated tractability from in vitro screening to in vivo behaviour7. Furthermore, bringing ideas to reality involves additional logistical challenges. Key concerns such as manufacturability and cost of goods aren’t typically at the forefront of academics minds, but are a determinant of progression towards patients. In terms of actions to be taking, I believe academics and industry need to be more open and willing to enter into scientific collaborations with one another. Whilst sometimes tricky to establish, they can be very revealing and effective at improving transparency. During my time in in AstraZeneca we have been involved in an industry-academic partnership called FoRmulaEx that formed a framework for interaction and collaboration between several universities and companies across Sweden. This has been very effective, and more of the outcomes and collaborative research generated can be found on the centre website8.
Michael: I think there is a disconnect between making those brilliant discoveries and the layers of complexity that inevitably come into play as you scale to whole organisms and towards the clinic. In vitro experiments are very ‘clean’ and can greatly simplify systems down to individual cell types, which can be great for studying particular events in isolation and building understanding. However, the whole body is a complex environment with additional physical barriers and interplays between organs and cells that are difficult to model or predict. Translating in vitro to in vivo findings is notoriously difficult, no matter the drug modality. We have been applying in vitro screening coupled with design of experiment and machine learning approaches to try and understand what features are important for efficacy and demonstrated tractability from in vitro screening to in vivo behaviour7. Furthermore, bringing ideas to reality involves additional logistical challenges. Key concerns such as manufacturability and cost of goods aren’t typically at the forefront of academics minds, but are a determinant of progression towards patients. In terms of actions to be taking, I believe academics and industry need to be more open and willing to enter into scientific collaborations with one another. Whilst sometimes tricky to establish, they can be very revealing and effective at improving transparency. During my time in in AstraZeneca we have been involved in an industry-academic partnership called FoRmulaEx that formed a framework for interaction and collaboration between several universities and companies across Sweden. This has been very effective, and more of the outcomes and collaborative research generated can be found on the centre website8.
NanoSphere: If there’s one key message or insight you’d like to share with readers about the future of nanomedicine, what would it be?
Michael: Endosomal escape in nanomedicines isn’t a novel problem, it’s just a new chapter of our cellular defence against invading material. Studying and learning from natural mechanisms will likely be key to future breakthroughs.
Michael: Endosomal escape in nanomedicines isn’t a novel problem, it’s just a new chapter of our cellular defence against invading material. Studying and learning from natural mechanisms will likely be key to future breakthroughs.
Michael`s references
- Wittrup, A. et al. Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown. Nat Biotechnol 33, 870–876 (2015).
- Munson, M. J. et al. A high-throughput Galectin-9 imaging assay for quantifying nanoparticle uptake, endosomal escape and functional RNA delivery. Commun Biol 4, 211 (2021).
- Joubert, F. et al. Precise and systematic end group chemistry modifications on PAMAM and poly(l-lysine) dendrimers to improve cytosolic delivery of mRNA. Journal of Controlled Release 356, 580–594 (2023).
- Addgene Galectin-9 Plasmid: https://www.addgene.org/166689/
- Kaur, N. et al. TECPR1 is activated by damage‐induced sphingomyelin exposure to mediate noncanonical autophagy . EMBO J 42, (2023).
- Bates, S. M. et al. The kinetics of endosomal disruption reveal differences in lipid nanoparticle induced cellular toxicity. Journal of Controlled Release 114047 (2025) doi:10.1016/j.jconrel.2025.114047.
- Hanafy, B. I. et al. Advancing Cellular-Specific Delivery: Machine Learning Insights into Lipid Nanoparticles Design and Cellular Tropism. Adv Healthc Mater 14, (2025).
- 8. FoRmulaEx Centre Information: https://www.chalmers.se/en/centres/formulaex/research/