AKNOWLEDGEMENTS

This study was carried out between 1994 and 1999 in the Department of Neurology, the research laboratory at Meilahti Hospital, and the Department of Pathology, Haartman Institute, University of Helsinki. I warmly thank Professors Jorma Palo and Eero Saksela for the excellent research environment and advanced facilities. I extend my thanks to the Department of Otolaryngology, where Professor Ilmari Pyykkö created a researcher-friendly atmosphere.

I thank Jorma Palo, Professor of Neurology, a scientist and writer, for convincing me that neurology was my field. During my residency, Jorma aroused my interest in neurofibromatosis and led me to the world of genetics of neurological diseases.

I am grateful to Professor Leena Palotie and Docent Aarno Palotie for initiating me into molecular genetics (far from squash courts) and their high spirit in scientific work. Leena Palotie´s '24-hour open lab' with always someone there is an unforgetful experience. I heartily thank all the members of the Palotie lab at the National Institute of Public Health. Aarno, always kind and encouraging, kept me going even through difficult times. Thanks to Aarno and Dr. Pekka Nokelainen who got me to 'understand' linkage analysis.

Then came along neurosurgeon Juha Jääskeläinen and others in the acoustic neuroma research group, Professor Ilmari Pyykkö and Docent Göran Blomstedt. I thank all of you for giving me the opportunity to plunge into neurofibromatosis 2. I thank you, Juha, for guiding me with this thesis, impulsively, but with focus. I thank also neuroradiologist Oili Salonen and neuro-ophthalmologist Kirsi Setälä, who taught me how scientific clinical studies are carried out.

I learned to appreciate the neurosurgical perspective to research through my dear collaborator Dr. Matti Seppälä, as well as Dr. Juha-Pekka Antinheimo and Dr. Mika Niemelä.

After clinical studies, it was merlin's turn. In this work, I am most grateful to Docent Olli Carpén, the second supervisor of this thesis, for his guidance into the cell biology of merlin. I have always enjoyed your company, as well as Juha's; your friendship has made the long work worthwhile. I thank Dr. Fang Zhao for his never-failing support and help with the merlin project. I never forget the dark-room techniques. I thank Leena 'scrambled peptide' Heiska and Mikaela 'yeast-two-hybrid' Grönholm for their collaboration and great spirit in the 'Olli lab'. I am also grateful to other Olli's crew members on this voyage: Nina von Numers, Olli-Matti 'night-shift' Mykkänen, Paula 'myotilin' Salmikangas, Anu 'smile' Taivainen, Emma Lindell, Heli Suila, Maciej Lalowski, and Luca Mologni. Olli does indeed need a bigger ship.

Apart form Olli's gang, I want to express my gratitude also to the other members of the ezrin-merlin group. This group was gathered together by the Virology Professor Antti 'father ezrin' Vaheri, and included Ossi 'departed son' Turunen, Tuomo Timonen, Päivi Majander-Nordenswan, Tom Böhling, Antti Salminen, Toni Järvelä, Eeva Auvinen and Torsten Wahlström. Special thanks go to Ossi and Tuula Helander for the profound conversations on all topics. Thank you all for creating an inspiring research atmosphere, where also humour played a role.

I thank Professor Matti Haltia for his collaboration in the nervous system tumour studies. I appreciate his accurate work and his wonderful personality. Also, I thank Dr. Minna Pöyhönen for her great interest and experise on neurofibromatoses.

I thank my collaborators abroad, Professor Tom Strachan from the University of Newcastle-upon-Tyne, and his lab members, especially Dr. David Bourn, for providing research facilities and help in an intensive short-term NF2 mutation study. I remember your hospitality with warmth, and recall the beautiful scenery at the mouth of Tyne. I appreciate the contribution of Professor Ellen Zwarthoff, as well as Drs. Michael den Bakker and Peter Riegman from Rotterdam, the Netherlands. I am thankful to my collaborators, Guy Rouleau and Mohini Lutchman, in Monteral, Canada, for providing valuable merlin antiserum.

During this long period of hard work, I received help from the technical staff of the Neurology research lab, especially Kaija Lindberg and Kati, among others on the first floor, and Aarno's lab at Meilahti Hospital. I am indebted to Ms. Hannele Pihlaja, the soul and the super 'teacher' technician of the Neurology lab. She was always eager to tackle innovations. I am also grateful for the invaluable help of expert technicians Tuula Halmesvaara, Mona Mäntylä, Tuula Niilola and Leena Harju at the Pathology Department. I appreciate the help of Lea Pylkkänen, Dr. Sebsebe 'ethiopian' Woldesenbet, and I am grateful to Virpi Tiilikainen for her skills in organizing practical things. Mr. Ben 'hardware' Roimola and Mr. Antti 'software' Huittinen of the Haartman Institute also deserve my warmest thanks.

I want to thank all my colleagues and other co-workers for the many good times at the Department of Neurology and Pathology. Especially, I am grateful to Pentti Tienari for his humane perspective to science and for his encouragement. Also, I have enjoyed the humour of neurologist Lauri Soinne. Our dilemma "why does our scientific work progress so slowly?" is left for the next generation to solve.

Docent Helena Pihko and Professor Juha Peltonen are gratefully acknowledged for reviewing and improving the manuscript of this thesis. I am also grateful to Ms. Terttu Kaustia for revising the English of this thesis.

I thank the head of the Department of Occupational Medicine at the Finnish Institute of Occupational Health, Professor Kaj Husman, for providing me the opportunity to finish this work. I am especially grateful to Dr. Kiti Müller, who for the last squeeze, harnessed me with blinkers and provided the isolation room. Also, I appreciate the support of my colleagues, Helena Huhmar and Hannu Laaksovirta, and all the members of the Neuroscience section. I thank Janne Muhonen and Aira Lindeman for library assistance.

I want to express my ultimate and most heartfelt thanks to my family, Irene, Tatu, Samuli and Aino, for their support and patience during the long work process. Though physically present, sometimes I must have been spiritually at work. I am deeply grateful to my morther-in-law, Meeri, and Stig for the innumerable times they have offered us their help.

I wish to thank my mother, Liisa, for her high values in life and her gentle encouragement toward academic achievements, and my father, Pertti, for his persistence and 'civil courage' to fight for justified values.

This study was supported by the Finnish Cancer Organizations, the Paulo Foundation, the Neurology Foundation, the Maire Taponen Foundation and the Academy of Finland.