UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl)
UvA-DARE (Digital Academic Repository)
Isovaleric acidemia: an integrated approach toward predictive laboratory
medicine
Dercksen, M.
Publication date
2014
Link to publication
Citation for published version (APA):
Dercksen, M. (2014). Isovaleric acidemia: an integrated approach toward predictive laboratory
medicine.
General rights
It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s)
and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open
content license (like Creative Commons).
Disclaimer/Complaints regulations
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please
let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material
inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter
to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You
will be contacted as soon as possible.
Acknowledgements
(Dankwoord)
Appendix
194
Thank you to each and every one who has guided and supported me through my PHD journey. I feel that I have learned so much about our field of biochemical research and it has been an honor to have worked amongst truly gifted scientists. I would like to thank God for giving me the ability, passion and perseverance to perform the research which I truly believe will change the lives of patients with inborn errors of metabolism.
I want to express my gratitude toward the "Koninklijke Nederlandse Akademie van Wetenschappen" for awarding me the Carolina MacGillavry PhD Fellowship which made this study possible. In addition, this study would not have been feasible without the participation of the South African IVA patients and families. They were unquestionably the center of attention in this study and we value their contribution immensely.
I would like to thank my promoters, Prof Ronald Wanders, Dr Ries Duran and Prof Carools Reinecke, for their continuous direction throughout my study. You had a tremendous impact on my scientific experience and personal life. Ronald, your unwavering support and faith in me and in my scientific endeavors will surely be remembered. You are a true inspiration in our field of biochemical research and I feel blessed to have had the opportunity to have worked with you. I admire your appreciation of my "out of the box" approach toward experiments. Your suggestions and critical evaluation toward my work contributed to the successful implementation of new and creative ideas (I also want to thank you and Elly for your hospitality and friendly advice whenever I needed it). Ries, your calm and collected approach toward research ideas and problems kept me positive (and sane!) throughout my study. I appreciate your understanding of the practice of science in South Africa – this always made me feel right at home. I will always admire your vast knowledge of the metabolism. Prof Carools, your constant motivation and attention to detail resulted in research outputs of the highest quality. Your knowledge of metabolomics was ultimately needed to make this study a success. All three of you have brought out the best in me and taught me to never give up. I always felt honored to be your student and I hope you are proud of me today. I truly wish that we can continue our collaboration.
This study would not have been possible without collaborators and co-authors sharing their knowledge and expertise in biochemistry and nutrition which ultimately resulted in publications. This multidisciplinary approach would not have been possible without the expertise of Dr Gerhard Koekemoer (in conjunction with the statistical consultation services at NWU). Our collaboration resulted in a bioinformatics contribution of the highest quality. I would like to express my appreciation to Prof Japie Mienie, Dr Lorna Jacklin, Dr Tuschka Reynders and Sister
Hester van der Bergh as well as AMPATH for their contributions and support during the IVA information day in September 2009. In addition, I want to direct my gratitude toward Prof Graham Baker and Elisabeth Lickindorf for their guidance in English grammar and the writing of scientific papers. Also, thank you to Christel Eastes for the meticulous language editing and help in the layout of the thesis.
To my Netherland colleagues and friends:
Maddy, your unlimited friendliness and positive mind-set motivated me throughout my 5 year journey. Your facilitation in the correspondence process to and from Amsterdam and Potchefstroom as well as your assistance in administrative responsibilities definitely saved the day(s). I appreciate your constant care and love during periods of joy, uncertainty and illness.
Jos, your knowledge in enzymology and β-oxidation guided my vision into new diagnostic possibilities. Your positive approach and calm words gave me confidence in performing enzyme assays, which was totally out of my comfort zone (remember to bring Mirjam and the kids to see the wild animals of SA – you promised!). Petra, thank you for your willingness to always assist in any type of problem I had (scientific and personal). I enjoyed our talks about our furry feline friends and hope we will stay in touch. I also appreciate your and Patricia's help with the culturing of the IVA fibroblast as well as your assistance in other diagnostic projects outside the scope of my PHD. I would like to thank Mirjam for her assistance in the enzyme assays as well as in "matters of the heart", and Connie for her expertise in immunoblot analysis. Thank you Jeroen for being my "lab buurman", I enjoyed your beautiful photographs of your pets and the Netherlands.
Lodewjik, I think I gave you a few extra grey hairs during these past few years. Thank you for your patience with difficult as well as "elementary" questions and my unorthodox ideas. I will always remember to apply your figure- and legend expertise when writing a paper. I sincerely enjoyed our Dutch-Afrikaans conversations and hope that we will have more in the future. Tom (Lodewijk's "wing-man"), thank you for your help in the production of the purified NAGS for in vitro assays. A large part of my study would not have been possible without this component. I enjoyed your enthusiasm when we talked about our beloved South African sport, rugby. Furthermore, a big thank you goes out to Rob for his help in the lab as well as with figures featured in this thesis.
This study would not have been a success without the guidance of the mass spectrometry group. Arno - we both had the same ideas when it came to the improvement of the NAGS assay and this made me believe in my approach. Thank you for your assistance and for fitting me into the busy MS schedule due to my time
Appendix
196
limitation (I have to say that I just love ion-paring!). I thank the whole group for letting me work with you on the highly sophisticated instrumentation – I truly learned a lot. I would like to thank all other colleagues from the different sections of Lab GMZ for their constant friendliness and assistance. A special word of thanks to the secretariat (including Gerrit Jan for managing the money from the Carolina MacGillavry fellowship fund), as well as colleagues from the balie and diagnostic laboratory who assisted in logistics and metabolite analysis, respectively. I want to express gratitude to the DNA diagnostic team for their assistance in the genotyping of the IVA patients. Thank you to Nico, Sascha, Fred and Wim for their willingness to help with PHD related questions as well as giving their insight into unique metabolic cases from South Africa. In addition, I would like to express my gratitude toward Eva Hartkamp from the international student office of the AMC, for organizing my working permit as well as temporary accommodation in Amsterdam.
To my fellow PHD compatriots: You all were and still are perfect examples of individuals with ultimate endurance. I felt honored to have worked beside gifted post-grads who were always willing to assist in any type of situation. Forgive me if I do not mention everyone's names. Please know that you all had a significant impact on my life journey and I will treasure these memories always. Paula, your caring personality gave me strength and the willingness to pursue my ideas which ultimately lead to the survival of my PHD. It was real nice to have a sympathetic ear when times were tough and to celebrate when we succeeded in our scientific endeavors. I truly miss you a lot. Sara, your friendship means the world to me. Your knowledge and application of enzymology made me realize how valued our field of research is. I just love your "big hug" messages. I hope that you, me and Paula will one day be able to have an extended visit and look back on the good old days.
Merel, you were one of my idols during my PHD study. I admire your endurance towards perfection. Your caring manner in solving problems (scientific and emotional) carried me through difficult times. Your works on peroxisomal disorders were and still are inspiring. I know that you will have great success as a biochemical geneticist. Odette, thank you for being the party spirit at the lab – you always lightened up the room with your sunny personality. Catherina, thank you for always being attentive, no matter how small the victory or the defeat. Thank you for the warm cups of tea and scheduled movie outings.
My PHD study would not have been possible without my support system in South Africa. Ek wil 'n "Afrikaanse Dankwoord" aan almal rig vir hul ondersteuning en omgee op alle vlakke van my lewe. Ek wil dank betuig aan verskeie mentors wat bygedra het tot my liefde vir biochemie. Ek wil spesifiek dankie sê aan Prof Japie (my metabolisme mentor en lab "vader"), Francois (my mentor in ensiemologie en
proefleser) en Chris (onvoorwaarlike ondersteuner en mede-idealis) - jul onderskraging en leiding op verskeie gebiede het groot drome moontlik gemaak. Ansie, jy's voorwaar 'n spesiale vriendin wat altyd in my geglo het en met een drukkie alles beter kon maak. Ek wil jou, en prof Japie, bedank vir die uitsonderlike manier waarop jul my bemoedigend bygestaan het en saam feesgevier het as mylpale behaal is. Dit is werklik 'n eer om saam met julle te werk. Verder wil ek dankie sê aan Elize vir haar positiewe energie en haar grappies wat vir daaglikse vreugde gesorg het. Jy is werklik 'n kosbare vriendin wat my altyd in jou gebede opgedra het (dankie ook aan Brian vir sy toesig oor my fisiese welstand). Ek bedank ook al my kollegas by PLIEM en NBS vir die tydelike oorname van my werksverantwoordelikhede en hul praktiese en emosionele bystand. Brenda, by jou het ek organiese sure leer interpreteer, min wetend dat dit die raamwerk sou vorm vir my PHD studie. Dankie dat jy altyd saam met my bly was oor goeie nuus al moes ons soms mekaar se trane afdroog in moeilike tye. Ek wil oplaas my waardering uitspreek teenoor almal in die departement biochemie vir jul ondersteuning (op verskeie vlakke) en geloof in my. Julle is "awesome"!
Met die ondersteuning van familie en vriende (buite die werk) kon ek na die sterre reik en my drome bewaarheid. Jean - my "partner in crime" – ons moes mekaar motiveer om ons nagraadse studies te oorleef en saam het ons dit voltooi. Jou ontspanne benadering tot die lewe en jou kunssinnige uitkyk op wêreld het my oë oopgemaak vir nuwe moontlikhede. Jy is my BFF en mag ons saam nuwe hoogtes bereik. William - AKA Jean’s Willow – thank you for your contagious positive attitude towards life, this gave me a new outlook on my journey. Marelize – jy was voorwaar my steunpilaar tydens my PHD studies. Jy was en is altyd bereid om te luister en met jou motivering het ek my kop omhoog gehou en volhard na die eindstreep.
Geen woorde kan my liefde en waardering teenoor my familie beskryf nie. Jul geloof in my was en is onwrikbaar. Dankie Pappa dat jy 'n toonbeeld van sukses deur harde werk vir my is. Jou finansiële ondersteuning gedurende my voor- en nagraadse studies word opreg waardeer. Ek hoop om nog veel dinge in my lewe met jou te deel. Mamma, jou gebede het my gedra deur goeie en moeilike tye. Jou blydskap oor elke hoogtepunt was altyd opreg en jou liefde vir my was en is nimmereindigend – dankie daarvoor. Ook wil ek dankie sê aan oom Len wat altyd in my vermoëns bly geglo het. Jou realistiese sienings oor dinge in ons wêreld het bygedra tot my analitiese denkwyse – die lewe is voorwaar vol potensiële vraagtekens wat hunker na oplossings! Rasionele en positiewe denke was nodig gedurende die 5 jaar en sonder my ma Marie sou dit nie moontlik gewees het nie. Motivering is definitief jou forté! Jy is 'n ystervrou wat enige probleem piepklein laat lyk. Ek is voorwaar lief vir jul almal.
Appendix
198
Laaste maar definitief die belangrikste is my liefste man, Tiaan. Ek sal nooit genoeg kan dankie sê vir wat jy vir my beteken het nie. Die laaste 5 jaar was definitief ‘n "roller-coaster ride" en soms moes jy maar net onvoorwaardelik liefhê, troos en selfs harde woorde spreek om my gefokus te hou op die einddoel. Jy het geglo (en glo steeds) dat ek enige taak kan bemeester en ek is trots daarop dat ons saam die PHD eindstreep gehaal het. Jy is my rots waarop ek altyd kan staatmaak en ek sien uit om ‘n toekoms vol avonture saam met jou te deel.
Dank u wel, en Totziens Marli
