6.1 Declaration of authenticity Erklärung nach §6 Abs.2 Nr.7:
Hiermit erkläre ich, dass ich die Dissertation
The role of MCPIP1 in insulin-secreting cells: comparison with SPL and HC mechanisms of action
selbstständig verfasst habe. Bei der Anfertigung wurden alle benutzten Hilfsmittel, sowie eventuelle Hilfedienstleistungen Dritter oder herangezogener Institutionen vollständig angegeben. Ich habe keine entgeltliche Hilfe von Vermittlungs- bzw.
Beratungsdiensten in Anspruch genommen. Niemand hat von mir unmittelbar oder mittelbar entgeltliche Leistungen für Arbeiten erhalten, die im Zusammenhang mit dem Inhalt der vorgelegten Dissertation stehen.
Ich habe die Dissertation an folgender Institution angefertigt:
Institut für Klinische Biochemie Medizinische Hochschule Hannover Carl-Neuberg-Straße 1
30625 Hannover
Die Dissertation wurde bisher nicht für eine Prüfung oder Promotion oder für einen ähnlichen Zweck zur Beurteilung eingereicht. Ich versichere, dass ich die vorstehenden Angaben nach bestem Wissen vollständig und der Wahrheit entsprechend gemacht habe.
____________________________ ____________________________
Ort, Datum Karolina Tyka
Annexes
6.2 Curriculum vitae
Personal Details
Name: Karolina Tyka
Date and place of birth: 19 February 1989, Gorlice, Poland
Nationality: Polish
Current address: Calenberger Straße 11
30169 Hannover, Deutschland E-mail address: Tyka.Karolina@mh-hannover.de
karolina.tyka@gmail.com
Mobile: 0049 1590 4023706
Studies and Education
10/2011 - 06/2013 Jagiellonian University, Cracow, Poland Master of Science in Biotechnology
Master Studies at the Faculty of Biochemistry, Biophysics and Biotechnology; Jagiellonian University, Cracow Poland; Master thesis: “Preparation and characterization of a genetic construct for the specific MCPIP1 overexpression in porcine adipose tissue”, final grade:
very good
Scientific supervisor: Prof. Dr hab. Jolanta Jura
10/2008 – 06/2011 Jagiellonian University, Cracow, Poland Bachelor of Science in Biotechnology
Bachelor Studies at the Faculty of Biochemistry, Biophysics and Biotechnology; Jagiellonian University, Cracow Poland; Bachelor thesis: “Effects of quercetin on the proliferation and viability of rat prostate cancer cells”, final grade: good
Scientific supervisor: Dr hab. Jolanta Sroka
09/2005 – 06/2008 General Secondary School No 1 in Gorlice, Poland Abitur, final grade:1.5
Class with extended educational programme of biology and chemistry
Professional Experience
since 10/2014 Hannover Medical School, Institute of Clinical Biochemistry
Doctoral candidate
10/2011 – 06/2013 Jagiellonian University, Institute of General Biochemistry, Cracow, Poland
Student assistant
10/2008 – 06/2011 Jagiellonian University, Institute of Cell Biology, Cracow, Poland
Student assistant Doctorate
since 10/2014 Hannover Medical School, Institute of Clinical Biochemistry
Doctoral thesis: “The role of MCPIP1 in insulin-secreting cells: comparison with SPL and HC mechanisms of action”
Scientific supervisor: PD Dr. rer. nat. Ewa Gurgul-Convey
Annexes
6.3 List of publications
1. Tyka K., Jörns A., Turatsinze J.V., Eizirik D., Lenzen S., Gurgul-Convey E.
(2019) MCPIP1 regulates the sensitivity of pancreatic beta-cells to cytokine toxicity. Cell Death & Disease 10 (1):29
2. Hahn C*., Tyka K*., Saba J.D., Lenzen S., Gurgul-Convey E. (2017) Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity. J Biol Chem 292 (49) 20292-20304
3. Scullion SM., Hahn C., Tyka K., Flatt PR., McClenaghan N.H., Lenzen S., Gurgul-Convey E. (2016) Improved antioxidative defence protects insulin-producing cells against homocysteine toxicity. Chem Biol Interact. 25 (256) 37-46
* shared first authorship
6.4 Conference contributions
1. Tyka K., Lenzen S., Gurgul-Convey E. (2016) MCPIP1-Überexpression reguliert die Insulinbiosynthese und glukoseinduzierte Insulinsekretion in insulinproduzierenden Zellen, poster presentation at the 52th Annual Meeting of the German Diabetes Association (DDG), Hamburg, Germany
2. Tyka K., Lenzen S., Gurgul-Convey E. (2016) The role of MCPIP1 in insulin-producing cells, poster presentation at the 51th Annual Meeting of the EASD, Munich, Germany
3. Tyka K., Lenzen S., Gurgul-Convey E. (2015) MCPIP1 Überexpression schützt insulinproduzierende Zellen gegenüber zytokin-induzierter Toxizität, poster presentation at the 50th Annual Meeting of the German Diabetes Association (DDG), Berlin, Germany
4. Hahn C., Tyka K., Lenzen S., Gurgul-Convey E. (2015) Sphingosine-1-Phosphat-Lyase und zytokinvermittelter ER-Stress in insulinproduzierenden INS1E Zellen, poster presentation at the 50th Annual Meeting of the German Diabetes Association (DDG), Berlin Germany
6.5 Contribution to publications
1. Eigenanteil an der Publikation „MCPIP1 regulates the sensitivity of pancreatic beta-cells to cytokine toxicity“ Tyka et al Cell Death Dis 2019:
Abbildungen: Fig.1 (alles außer A - human islet data),2,3,4,5,6 (alles außer A - human islet data),7 (teilweise A und B, vollständig selber gemacht C), Tab.S1, Tab.S4, Fig.S1, S2, S3
Textpassagen: Introduction, Methods, Results (Para 1,2,3,4,5,6,7,8,9), Revision of MS Experimentelle Expertise:
• Cloning
• RNA Isolierung, cDNA Synthese und real-time RT-PCR
• Transfektionen und Generierung von allen Zellklone
• Inkubationen mit Zytokinen und anderen Reagenzien
• Zytokintoxizität (MTT assay, Caspase-assay, ATP-Gehalt Messung,Proliferation usw)
• Nitrooxidativer Stress (NFkB-SEAP, iNOS, Nitrit)
• Immunfluoreszenz (INS1E-Zellen)
• Western Blot Fragestellung:
Die Rolle von MCPIP1 in pankreatischen Beta-Zellen nach Inkubationen mit Zytokinen
2. Eigenanteil an der Publikation „Overexpression of sphingosine-1 phosphate lyase protects insulin-secreting cells against cytokine toxicity“ Hahn et al JBC 2017:
Abbildungen: Fig.2 - rat islet data, Fig.4 E,F,H,I,J,K,L,M
Textpassagen: Para Nr.6, 7 und 8 Ergebnisse (Results section), Revision of MS Experimentelle Expertise:
• Real-Time RT-PCR Messungen von Effekten von Zytokinen auf SPL Expression in Ratteninseln
• Real-Time RT-PCR Messungen von Effekten von SPL-Überexpression auf BIP, CHOP, Sec61a und mitochondrialen Chaperonen (Mimitin und PHB2) in unbehandelten und mit Zytokinen inkubierten Zellen
• Western Blot Analyse von PHB2 Expression
• Knockdown von PHB2 in INS1E Zellen incl. Messungen von Zytokintoxizität Fragestellung:
Die Bedeutung von SPL für ER-Stress und Mitochondrialen Stress in Beta-Zellen nach Inkubationen mit Zytokinen
Annexes
3. Eigenanteil an der Publikation “Improved antioxidative defence protects insulin-producing cells against homocysteine toxicity” Scullion et al Chem Biol Interact 2016
Abbildungen: Fig.5 B und D Textpassagen: Revision of MS Experimentelle Expertise:
• Glucoseinduzierte Insulinsekretion (GSIS) nach Inkubation mit HC oder Cys in Anwesenheit oder Abwensenheit von Alloxan
Fragestellung:
Die Bedeutung von HC/Cys für GSIS in Beta-Zellen und Alloxan-vermittelten GSIS-Inhibierung
6.6 Acknowledgements
First of all I am deeply grateful to my thesis supervisor PD Dr. Ewa Gurgul-Convey for the continuous support of my doctoral study and research, for her patience, motivation, enthusiasm, and immense knowledge. Her guidance helped me in all the time of research and writing of this thesis, for which I am extremely grateful. The door to her office was always open whenever I had a problem with my experiments or a question about my research.
I would like to thank Prof. Dr. Sigurd Lenzen for giving me the opportunity to perform my dissertation at the Institute of Clinical Biochemistry. I am grateful for all his valuable suggestions and contribution to the progress of my work. Additionally, I wish to express my gratitude to Prof. Dr. Anne Jörns and Prof. Dr. Helmut Holtmann for their tremendous knowledge and assistance.
A very special gratitude goes out to the DAAD Foundation for awarding me with the scholarship for the doctoral students in Germany for the entire time of my project.
Completing this thesis would have been much more difficult without the support and friendship provided by the other members of the Institute of Clinical Biochemistry at Hannover Medical School. In particular, I would like to thank Anna, Brenda, Thomas, Hanna, Martin and Maren for creating a supportive and amiable atmosphere of work.
Long days in the lab would not have been the same without you. Matthias, Stephan, Ilir, Ulf and Ortwin-thank you for all professional comments and help you provided to me during the performance of my experiments.
Finally, I would like to thank my family and friends for supporting me during my whole studies, especially my parents and siblings for their continued help and encouragement.
Without you, none of this would have been possible. Special thanks to my best friends Iwona and Arek who experienced all of the ups and downs of my research. Thank you for your friendship and emotional support during the difficult times. Last, but not least, I want to express my deeply-felt thanks to Daniel for his unconditional support, help, patience and for making me feel in Hannover at home. Thank you for always being there for me and believing in me.