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University of Groningen Analysis of the ATCase catalysis within the amino acid metabolism of the human malaria parasite Plasmodium falciparum Bosch, Soraya Soledad

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University of Groningen

Analysis of the ATCase catalysis within the amino acid metabolism of the human malaria

parasite Plasmodium falciparum

Bosch, Soraya Soledad

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.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2019

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Bosch, S. S. (2019). Analysis of the ATCase catalysis within the amino acid metabolism of the human malaria parasite Plasmodium falciparum. University of Groningen.

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Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.

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List of publications

1. Batista FA*, Bosch SS*, Lunev S, Meissner KA, Butzloff S, Linzke M, Romero A, Wang C, Muller I, Dömling I, Groves MR and Wrenger C. (2018) Oligomeric Protein Interference Validates Druggability of Aspartate Interconversion in Plasmodium

falciparum. MicrobiologyOpen. (2018) DOI: 10.1002/mbo3.779. *Authors contributed

equally.

2. Lunev S*, Bosch SS*, Batista FA, Wang C, Li J, Linzke M, Kruithof P, Chamoun G, Dömling A, Wrenger C, Groves MR. (2018) Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase. Biochemical and Biophysical Research Communications (BBRC). DOI: 10.1016/j.bbrc.2018.02.112. *Authors contributed equally.

3. Lunev S, Batista FA, Bosch SS, Wrenger C and Groves MR. (2016) Identification and Validation of Novel Drug Targets for the Treatment of Plasmodium

falciparum Malaria: New Insight. Book Chapter.

DOI: 10.5772/65659

4. Lunev S*, Bosch SS *, Batista FA, Wrenger C and Groves MR. (2016) Crystal structure of truncated Aspartate Transcarbamoylase from Plasmodium falciparum. Acta Crystallogr F Struct Biol Commun. DOI: 10.1107/S2053230X16008475. *Authors contributed equally.

5. Bosch SS*, Kronenberger T*, Meissner KA*, Zimbres FM*, Stegehake D, Izui

NM, Schettert I, Liebau E, Wrenger C. (2015) Oxidative Stress Control by Apicomplexan Parasites. BioMed Research International. *Authors contributed equally.

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6. Bosch SS*, Lunev S*, Batista FA, Wrenger C, Dömling A, and Groves MR. (2019) Molecular target validation of Aspartate Transcarbamoylase from Plasmodium falciparum by Torin 2. *Authors contributed equally. (SUBMITTED)

7. Batista FA, Gyau B, Bosch SS*, Lunev S, Chao W, Vilacha JF, Wrenger C and Groves MR. (2019) Protein Interference Assay (PIA) offers a novel venue towards the validation of antimalarial target candidates. *Authors contributed equally. (SUBMITTED)

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Acknowledgment

First I would like to thank my advisor Prof. Dr Carsten Wrenger. I am very grateful to have been part of his group and research, from the beginning Prof. Wrenger was helping a lot with the project, he has a huge vocation for science which is demonstrated in every conversation full of new ideas and projects. Besides, he trusted me and enrolled me in a double degree program between the University of Groningen and the University of São Paulo, where I learned a lot from the European system and culture. Along all these years he was a great example of compromise, responsibility and dedication; for these reasons, I only have gratitude with him.

Also, I would like to thank Porf. Dr Mathew Groves for the opportunity to perform crystallisation experiments in his lab at RUG, for accepting me in his group, for the patience and for giving me another point of view of the scientific world, with such a diverse group in the lab. I spent seven interesting months in The Netherlands. Moreover, my thanks to Prof. Dr Alexander Dömling and his group, first to support our project with all kind of synthetic compounds and second for making us trying new things such as “Hormigas Culonas” with chocolate.

Furthermore, I would like to thanks the professors from the assessment committee for the comments and corrections, Eva Liebau, Wim Quax, Frank Dekker and Gerhard Wunderlich; as well as my evaluation committee at USP Andrea Balan. Additionally, my thanks to the support staff from USP and RUG, especially to Silvia and Cathy. My thanks to all the people who past (and are) at the USP lab. First, to Ariel Silber's group, with whom we shared the lab in the first years, there were amazing people who contributed a lot to the knowledge and human part, especially to María Julia, Marcell, Raissa, Rodolfo and Alexandre. Second, to Carsten´s group wiht whom I spent my last five years, I learnt not only most of the techniques regarding my project, but also to respect and coexist with amazing people from all round the world, my special thanks to Kamila and Jasmin, who introduced me the parasite culture and related procedures. Also, I want to thank the group of Gerhard Wunderlich with whom we are nowadays sharing the lab and my special thanks to Rosana and Tatiane, thanks for your advices and support regarding the lab work, for the moments outside the lab, for the talks, the dinners, the

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wines together. Finally, my thanks to Claudio Marino´s lab, where we share the cell culture lab, especially to Erika and Douglas.

Moreover, I want to thank some random people whom I cross in this adventure, and they left me good memories and friends, Luciana, Anto migraña, Laura, Leila, Belen, Irina, Xiomara, Marise, Nico, Wenja, Kai, Alaa, Ameena, Paulinho, Maria, Olivia, Nick, Ismael, Claudia specially thanks to my first roommate Bruno and my aunt, Lili for all the postal she send me. Thanks a lot to my high school friends, Flor, Rolo, Nadia, Dani, Luci and Rocio. Also, to my university friends from Rosario, Sofia, Camila, Lucia, Mauricio and Andres, which were given me their support in moments of hesitation. Besides, I want to thanks Julia Cricco for her advices in this university career, without her contact I would not be here.

I sincerely want to thank MSc. Fernando Batista, he was my first and only student and afterwards, such a big support and friend during my stay in The Netherlands, we spent funny times trying to understand the Dutch culture and working together in unexpected contexts. I learned a lot from our daily routine inside the lab and from the time spent outside, when I was feeling like (my Brazilian) home. It was a pleasure, the collaborations, the trips to DESY for data collections, the advices and the company. Furthermore, I want to thanks Dr. Sergey Lunev. He was always taking care of my welfare since I arrived in Groningen. Although we had differences in carrying out the experiments, I learned a lot with him and to respect the different points of view. He is a more reserved person with a good heart. We also had funny moments here in São Paulo, as well as, in The Netherlands with Linda, both of them there were really kind.

Quiero agradecer enormemente a mi familia, a mi mamá Yoli, mi papá Enri y mi hermano Marco, ellos son mi principal apoyo. A pesar de que estamos separados físicamente la mayor parte del tiempo en estos últimos años, conseguimos disfrutar de cada minuto que pasamos juntos. Además quiero dedicarles este trabajo también a ellos, ya que me enseñaron a ser responsable y seguir adelante, así como también a que siga mis sueños a tal punto de poder trabajar en lo que me gusta hoy en día. Los extraño y los quiero mucho.

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minha colega de apartamento Dona Clementes! O tempo compartido com todos vocês me deixa muito feliz de saber que tenho o carinho de uma família maravilhosa. Muito obrigada pelos momentos compartidos!

Minha gratidão também com meus amigos de Socorro Laís, Hellen, Jonhy, Iris, Jairo, Paulinho, Uchi, Andreía, Marina e a turma inteira, foi excelente conhecer vocês, um grupo de boas pessoas super heterogêneas e cheias de boas energias.

Finalmente, gostaria de agradecer a Marcelo, o destino cruzou nossos caminhos no começo do doutorado e desde então que estamos crescendo juntos, passando por momentos inesquecíveis. Ele é meu companheiro, e agora também meu sócio de negócios, ele mostrou o mundo para mim desde outra perspectiva fazendo-me uma melhor pessoa todos os dias. Eu estou muito agradecida de compartir minha vida com ele.

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About the author

Soraya S. Bosch was born on the 18th of February 1988 in Reconquista, Argentina. After finishing the school in 2005, she started a Bachelor and Master degree in Biotechnology in March of 2006, at the University of Rosario (UNR). In 2010, in association with the biophysics department, she initiated her Master studies under supervision of Dr Pablo E. Tomatis and Prof. Dr Alejandro J. Vila as co-advisor. The title of the master dissertation was “Optimization of the hydrolytic capacity of the serine β-lactamase KPC by directed molecular evolution”. The objective of the project was to study the Serin-beta-lactamase, KPC-2. This protein has a high relevance nowadays in the clinic, because of its ability to hydrolyse carbapenems (antibiotics of the last defence line).

After defending the Master thesis in September of 2012, she worked as a technician in the Laboratory of Prof. Vila until she moved to São Paulo, Brazil to start a PhD with Prof. Carsten Wrenger, in August of 2013. The Soraya’ doctoral studies were focused on a protein called Aspartate Carbamoyltransferase of the malaria parasite Plasmodium

falciparum which she validated as a drug target by in vitro characterization of the protein

as well by in vivo experiments using the protein interference technique with transgenic parasites. Subsequently, thank to several negotiations and networking between the Universities of São Paulo and the Groningen, she initiated the PhD double degree program between São Paulo and Groningen and became the first Brazilian student who participated in the program.

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