Intra- and intercellular trafficking of the prion protein [Elektronische Ressource] / presented by Edwin Schiff

Edwin Schiff

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• Gesundheit

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• Publié par: universitat_regensburg
• Publié le: 01 janvier 2008
• Nombre de lectures: 86
• Langue: English
• Poids de l'ouvrage: 5 Mo

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UNIVERSITE PARIS VI-PIERRE ET MARIE CURIE
ECOLE DOCTORALE DE PHYSIOLOGIE ET PATHOPHYSIOLOGIE
UNIVERSITÄT REGENSBURG
NATURWISSENSCHAFTLICHE FAKULTÄT III-BIOLOGIE UND
VORKLINISCHE MEDIZIN
Year 2007
Dissertation
for obtaining the grade of Doctor of the University Paris VI and the University of
Regensburg
presented by
EDWIN SCHIFF
10.12.2007
Intra- and intercellular trafficking of the prion protein
Supervisors: Dr. Daniela Männel and Dr. Chiara Zurzolo
Thesis committee:
Mr. Korth Carsten Rapporteur
Mr. Lazarow Paul
Mrs. Rousset Monique Examiner
Mr. Tanner Widmar
Mrs. Männel Daniela Thesis supervisor
Mrs. Zurzolo ChiaraThe most exciting phrase to hear in science, the one that heralds new
discoveries, is not 'Eureka!' (I found it!) but 'That's funny ...'
Isaac Asimov
I was gratified to be able to answer promptly. I said I don't know.
Mark TwainAcknowledgements, remerciements, Danksagungen:
I would like to thank first of all my two supervisors.
Without Chiara’s drive, support and most importantly immense
patience with me, I wouldn’t be writing these acknowledgements for
my own thesis, because there wouldn’t be any. I know that it wasn’t
easy for her and she certainly grew a few grey hairs due to me. Sorry
for that. On the other hand, we also set free a lot of positive energy,
which ended in quite a good job, I think. I truly hope that we will
manage to bring the submitted manuscripts to a good end.
I am also deeply indebted to Daniela, whose confidence in me
allowed me to go to the Institut Pasteur in the first place. Her support
and calming words always found an open door and I am grateful for
having her as my other “doctor-mother”. I also wanted to thank her for
the financial help in the last months of my thesis. Would not have
worked without it.
I thank Prof. Widmar Tanner for giving me the opportunity to
enroll as a Ph.D.-student at the University of Regensburg. The few
times we met, he forced me to look at my work from a different angle,
which certainly helped to make it progress.
I also wanted to thank my two rapporteurs (yes, this is also an
English word).
I haven’t had the honour to meet Dr. Carsten Korth yet;
therefore I will thank him hereby for reading and evaluating my thesis
and for coming to Paris for my final exam. I’m looking forward to
talking to him.
Prof. Paul Lazarow was not only my tutor in a good journal-
club, but also fun to have one or the other beer with at our famous
TGIFs. I also wanted to thank him for his advice on the TNT-project.
Paul, you’ll have to listen to it one last time, so hang in there!
I would like to thank all the people from the Paris-lab who went
with me all the way. It is great to have kind people around you, who
laugh with you in good times and listen to you in bad times (jeez,
sounds almost like a marriage). In the course of these three years and
a bit, a few left and others have started anew. I wish them all simply
the best for their plans and wishes for the future.
I wanted to thank Philippe, the good soul of the laboratory, for
his help, patience and assistance with all the silly requests and
questions I had. Be it a check for exactly 4, 57! for my re-inscription at
Paris VI, his help for me getting web-access at home (quelle aventure!!)
or the discussions in the P2.
Thomas I wanted to thank for being all along my brother-in-
arms. I apologize once more to not have been able to attend to his
defence. I think that he is the only one in the laboratory to understand
the phrase “To have Hungarian blood”. Besides, Thomas and Philippe
were two of the few who allowed me to sharpen my French on them. I
must say they were poor teachers; my French still feels like a fish
trying to ride a bicycle.I am also indebted to all the wonderful ladies in the lab,
especially the prion-ladies. For some time I felt a little bit like Charlie
in “Charlie’s Angels”, but then Duncan came and spoiled it all. Zrinka,
Enza, Maria-Agatha, Jacquie, Anna and Stéphanie and the newly
arrived Karine are all delightful and great to work with, always
having a good scientific advice and willing to cope with my weird
sense of humour (yeah, they laughed…sometimes), moods and
outbursts of impatience. Additionally, some of them (Enza, Zrinka)
were always a good source for coffee—even though they didn’t know
about me taking theirs. Zrinka was also the one to teach me her very
own creation of a positive adjective (“bombastic”™), which I use now
on a regular basis. Enza and Maria-Agatha are really good friends in
the laboratory and outside of it. Due to them I really ameliorated my
Italian (I think); Maria-Agatha even kept on talking in Italian to me
despite of Chiara shouting from her office: “Speak English!”. Grazie
ragazze!
I would also like to thank Anna for her undwindling help and
flow of hippocampal neurons.
Stéphanie I have to thank for her support with the FRET-
experiments. I have the vague feeling that we’re not done with that yet,
so thank you in advance.
Last but not least I wanted to thank Duncan, whose arrival,
from one day to the other, let things turn the sunny side up. I am
deeply indebted to him for correcting my thesis and eradicating all the
“Edwinglish” from it, as well as doing the same for the TNT-
manuscript. If you, the reader, should find more typos or bad English
in this work, than he’s to blame and certainly not me.
Ich wollte mich auch noch bei Luise Kroher bedanken, die mir
stets aus der Ferne versucht hat weiterzuhelfen und es auch meistens
geschafft hat.
Desweiteren wollte ich mich bei Tina bedanken, für ihre positive
Einstellung, die tatsächlich manchmal auf mich abgefärbt hat. Tue es
weiterhin, bitte.
Mein größter Dank gilt meinen Eltern, die mir seit dem Beginn
meines Studiums mit unerschütterlichem Vertrauen treu zur Seite
standen. Ohne euch wäre nichts von dem hier möglich gewesen.I. ABBREVATIONS AND NOMENCLATURES UTILIZED ................................................................... 4
I.1: ABBREVIATIONS....................................................................................................................................... 4
I.2: NOMENCLATURE AND DEFINITION OF THE DIFFERENT FORMS OF PRP ................................................... 6
II. A BRIEF CHRONOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
(TSES)................................................................................................................................................................. 7
III. INTRODUCTION...................................................................................................................................... 9
III.1: ON THE NATURE OF PRIONS................................................................................................................... 9
III.1.1: Prions are not easily inactivated by ionizing radiation: Is it therefore an infectious protein?
.................................................................................................................................................................... 9
III.1.2: Prions: a viral agent?................................................................................................................. 12
III.2: TSE IN ANIMALS.................................................................................................................................. 14
III.2.1: Clinical signs of TSEs................................................................................................................. 14
III.2.2: The histopathology of TSEs........................................................................................................ 14
III.2.3: The main forms of TSEs.............................................................................................................. 15
III.2.3.1: Scrapie in sheep and goat .....................................................................................................................15
III.2.3.1.1: Description .........................................................................................................................................15
III.2.3.1.2: Susceptibility......................................................................................................................................16
III.3: BOVINE SPONGIFORM ENCEPHALOPATHY (BSE)............................................................................... 17
III.4: CHRONIC WASTING DISEASE (CWD)................................................................................................. 20
III.5: OTHER ANIMAL TRANSMISSIBLE ENCEPHALOPATHIES....................................................................... 21
III.6: HUMAN ENCEPHALOPATHIES .............................................................................................................. 21
III.6.1: The sporadic forms ..................................................................................................................... 22
III.6.2: Familial or hereditary prion diseases........................................................................................ 23
III.6.3: Acquired human TSEs ................................................................................................................ 25
III.6.4: Susceptibility to vCJD ...........