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University of Groningen Unravelling the mechanisms of recognition and internalization of nanoparticles by cells Montizaan, Daphne

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University of Groningen

Unravelling the mechanisms of recognition and internalization of nanoparticles by cells

Montizaan, Daphne

DOI:

10.33612/diss.136290962

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

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Publication date: 2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Montizaan, D. (2020). Unravelling the mechanisms of recognition and internalization of nanoparticles by cells. University of Groningen. https://doi.org/10.33612/diss.136290962

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Acknowledgements

Here, I am at the end of the PhD period, finishing the last bits. The four (almost five) years went unbelievable fast. I have known ups and downs, and learned about my limits. Most importantly, I have met and been among many incredible people. People who helped me get to this moment, and whom I would like to pay my gratitude to. First of all, I would like to thank my main supervisor, prof. Anna Salvati. Dear Anna,

the first time that we met was during a skype interview while I was in Australia for an internship. Your enthusiasm and openness were clear from the start and made me want to start a PhD with you. I cannot express how happy I felt when you offered me the position the second time we called. We were both ‘fresh’ in our new roles, and had to find our way at the beginning. Besides teaching me about the field, you showed me the other aspects of science (interviewing potential candidates, writing papers and its revisions, and the politics behind). You asking me to join the interviews for the PhD position of Hector and Post-doc position of Natasha made me feel valued. Thank you for your positive personality and always being there to help no matter what or what time ;-) I feel honoured to have been part of your starting group and hope we keep in touch. Also, special thanks to my other supervisor prof. Klaas Poelstra. Dear

Klaas, even though you were really busy as vice dean during most of my PhD, I got to know you better during the second part. You made time when needed and checked my thesis in the short time we had to finish it before the summer. Thank you for the advice on the progress of the PhD project and asking for my personal perspective and opinion. You made me realize that I am now (almost) an independent scientist. I would like to thank the assessment committee prof. Arwin Jones, prof. Raymond Schiffelers, and prof. Hidde Haisma for reading and approving my thesis. Also thank

you prof. Hidde Haisma for letting me work in your lab and giving me advice on the production of the retrovirus. Putting me into contact with prof. Jan Carette was essential for moving forward in my project.

Additionally, I would like to thank prof. Jan Carette, dr. Diana Spierings, prof. Victor Guryev, and dr. Christoffer Åberg for their contribution to the forward

genetic screening. Dear prof. Jan Carette, thank you for sharing the protocols of viral production and sequencing preparation, which were truly valuable for me to continue the screening. I am grateful for your willingness to share information. Dear Diana, thank you for taking the time to go through the sequencing protocol and help me understand the different steps. Dear Victor, your input and suggestions on the analysis of the sequencing data was treasured. Thank you. Dear Christoffer thank you

Acknowledgements

for your critical way of thinking and your suggestions (either directly or via Anna), such as sorting of non-mutagenized cells.

Next, I would like to thank the staff that worked in the group during my PhD project. Dear prof. Barbro Melgert, thank you for your advice on all

immunology-related matter, from creation of monocyte-derived macrophages, to suggestions on good immunology courses and interesting guests speakers for a potential seminar. Thank you prof. Geny Groothuis, dr. Leonie Beljaars and dr. Inge de Graaf for your

questions and suggestions during group meetings. Dear Gillian, you are the glue of

the department and can cheer everyone up with your stories. Thank you for checking up on me in the more difficult times, and arranging all things that seem so small but are so important to keep things running smoothly. Catharina, Eduard, Marina, and Ilse, while Gillian is there for the non-lab-related issues, you were always there to

keep the lab running. Dear Catharina, thank you for showing me the way around the lab and helping me with my large experiments. I enjoyed our chats about lab issues, family, or just the weekend, during the many hours that we were training our thumbs ;-) Your hard-working, honest, direct, and helpful attitude, made me know that I could count on you. Dear Eduard, you were always there to help out in between you running around the lab helping others, and performing your own experiments. Thank you for helping me in the lab and all computer-related issues. Kind Marina, unfortunately we did not have to opportunity to work together a lot, but whenever I had a question you always tried to help me. Thank you for that. Ilse, you just arrived when I was finishing my PhD, but you seemed to already understand part of my struggles during our first talk. I wish you lots of fun working in this group.

Of course no PhDer can be without fellow PhD and Post-doc colleagues which support each other, and which I would like to thank starting with the two fellow PhDers and friends who are my paranimphs. Lovely Roberta, I am so happy that we shared an

office from the first day I started almost till the end of the PhD. You made me feel ‘at home’ right away. Whenever I felt down, you made me feel better with your kind words and warm hugs. It is always a joy to be around you, because of your positive energy and kindness. Thank you for always being there for me and sharing important moments of my life (marriage, PhD defense). The office felt weird and sad the last couple of months when you had already finished. Luckily I know that even though our time as colleagues is over, our friendship will remain. Sweet Oly, I think you are the

kindest person I know. You are always thinking about others and putting them first. You pay attention to every small sign and react to it with a kind gesture. But please, do not forget about yourself. I am grateful that we have met and that you accepted the task of being my paranimph. Hang on, you will finish as well. And sensible Laura,

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Acknowledgements

completes the Ro-Da-Oli-La group. You are always so organized with your sticky notes and clear markings in various calendars. I admired your determination in all you do, and your creativity leading to beautiful presentations and to your very personal artistic thesis. It was really nice to hang out also outside of work and follow painting classes together. Also thank you for all the wise and useful advice you have given. We as the Ro-Da-Oli-La group have shared an important journey together and I know it does not stop here, but we will meet at many other occasions and places (like Mexico ;-)).

I felt also supported by all PhD and Post-doc colleagues from the Nano group who taught me a lot. Dear Valentina, when I arrived you were the ‘oldest’ PhD in the lab.

Together with your strength and determination, you were regarded as the wise and experienced one in the Nano group, and I remember the many times I went to you with questions. Thank you for the good discussions and your advice. Dear Keni, you always stayed friendly and your creativity was inspiring. You often came with creative solutions or alternative twists to projects. Many times you first asked your neighbour if a question was stupid before you asked it in public, but believe me Keni,

I never heard you ask a stupid question. I know you will get far in science with your hard-working and curious mindset. Dear Hector, I remember how nervous you were

during your presentation for the job interview, but then and later you showed time and time again how smart you are. I really got to know you better when we shared an office during the last year of my PhD. I loved to see you joining for lunch and getting involved in the conversations Roberta and me had. Thank you for being the rational man in the room and putting things into perspective. Dear Aldy, we are finishing

around the same time. By seeing you so calm under the circumstances, you showed me another point of view to doing a PhD. I hope you will find the job in industry that you want. Dear Harita, to me you appear to be calm no matter the circumstances. I do

not know how you do it. Your project including having three supervisors so far apart seems incredibly difficult to handle. This just shows how strong you are. I wish you the best of luck finishing your PhD. Dear Sarah, you were an exemplary colleague. I

do not know how you could stay so kind and helpful and still perform your own work. Even though it was for a short time, it was a joy to have you as a colleague and seeing the love you have for animals especially your beautiful cats. I really hope to stay in touch. Dear Natasha, starting in such a different environment (both place and topic)

must have been difficult but you grew fast. Your determination and mental strength are unprecedented. I do not understand how you combined your research, sports, and all other things you organized (stretching classes, setting up the CRS BeNeLux chapter, applying for industry jobs, etc). I would like to be able to manage as much as you do. Thank you for all the career advice.

Moreover, I would like to thank all the other colleagues from the department. Dear,

Fransien, Anienke, Shanshan, Gwenda, Adhy and Habibie thank you for your help

and advice either on the scientific or personal area. I wish you the best in finishing your PhD and/or your next career. Dear Sylvia, Natalia, Carian, Christina, Viktoriia,

and Andreia you were working in the department for longer and most of you were

add the end of your PhD when I arrived. Still, I remember the good atmosphere in the group to which you all contributed. Thank you for the social lunches and sharing of stories. I wish you good luck with your chosen paths.

Additionally, I would like to mention the master students I worked with: Valeria, Cat, and Mikhael, who also created part of the results found in this thesis. We had

some great time inside and outside the lab. I liked it when you questioned things that seemed normal to me, but made me think. Thank you.

Next, I want to pay my gratitude to the friends and family outside the lab that supported my personal well-being by making sure I enjoy life outside work. Dear

Katja and Matej, I am so happy that I went to Groningen for the PhD, so I met you

guys. It started with cosy dinners between neighbours in the tiny living rooms of the way too small improvised apartments that we rented. And now, living over a thousand kilometres apart, we both have another holiday destination where we can go on a beautiful hike or have a day full of cycling ;-). Thank you, Hugo & Paulien, Ingo & Pernille, and Harro & Kirsty for you the nice dinners, family holidays, good talks, and

life-advice. I feel lucky to have a loving family-in-law like yours.

And where would I have been without my parents, Arjan, and Melanie, who are always

there for me no matter what? I feel blessed to have such a kind, helpful, trustable, caring and loving family. You shaped me the way I am and gave me the strength to get to where I am now. Thank you mom and dad for your unconditional love. Thank you Arjan and Melanie for listening to my complaints and understanding me. Special thanks to Melanie who created the beautiful paintings for the cover and corrected my Dutch summary.

My second half, Jordi, without you the struggles would have been much heavier. You

were there to calm me when I worried, dry my tears, and remind me to come home not only physically but also with my mind. You help me push myself and grow, while still accepting me for who I am. Thank you for making my heart glow every day again.

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About the author

About the author

Daphne was born in 1992 in Geldrop the Netherlands. She followed her secondary school in Breda where she finished with honours. She continued studying ‘Molecular Life Sciences’ at Wageningen University during which she did two research projects in immunology. For one of the projects she arranged an internship at the Diamantina Institute (connected to the University of Queensland), Brisbane, Australia. She finished both her Bachelor and Master with honours. Because she likes the challenges and diversity of performing research, she continued with a PhD project on the endocytosis of nanoparticles at Groningen University. Daphne has always had a heart for animals and nature, and these play a large role in her daily life which is why this thesis is printed on recycled paper. She would like to continue her career by helping the development of life-saving treatments.

List of publications

Published

‘Interactions at the cell membrane and pathways of internalization of nano-sized materials for nanomedicine’ V. Francia*, D. Montizaan*, A. Salvati. Beilstein

J. Nanotechnol. 2020, 11, 338–353. doi:10.3762/bjnano.11.25

‘Comparison of the uptake mechanisms of zwitterionic and negatively charged liposomes by HeLa cells’ D. Montizaan*, K. Yang*, C. Reker-Smit, A. Salvati.

Nanomedicine: NBM (in press)

* equal contributions

Submitted or in preparation

‘Sources of Variability in Nanoparticle Uptake by Cells’ C. Åberg, V. Piattelli, D. Montizaan, A. Salvati. Manuscript submitted

‘Dynamic response of the pathways involved in nanoparticle uptake in a genome-wide time-resolved forward genetic screening’ D. Montizaan, V. Guryev, D. Spierings, A. Salvati. Manuscript submitted

‘Preparation and cell uptake of liposome and liposome-coated silica: effects of nanoparticle rigidity and role of curvature-sensing proteins’ D. Montizaan, C. Saunders, K. Yang, C. Montis, D. Berti, A. Salvati. Manuscript in preparation

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