{"id":6365,"date":"2026-10-19T09:48:49","date_gmt":"2026-10-19T09:48:49","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-romain-maurice-jacques\/"},"modified":"2026-10-19T09:48:49","modified_gmt":"2026-10-19T09:48:49","slug":"doktorsvorn-i-lif-og-laeknavisindum-romain-maurice-jacques","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-romain-maurice-jacques\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum – Romain Maurice Jacques"},"content":{"rendered":"
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\u00deri\u00f0judaginn 18. j\u00fan\u00ed 2024 ver Romain Maurice Jacques Lasseur doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: \u00c1hrif skilyrtrar st\u00f6kkbreytingar \u00ed Mitf geni m\u00fasar \u00e1 \u00feroskun og starfsemi litfruma. Role of Mitf in melanocyte development as determined by a conditional hypomorphic mutation.<\/p>\n

Andm\u00e6lendur eru dr. Richard Mort, d\u00f3sent vi\u00f0 Lancaster University \u00ed Bretlandi, og dr. S\u00e6var Ing\u00fe\u00f3rsson, d\u00f3sent vi\u00f0 Hj\u00fakrunar- og lj\u00f3sm\u00f3\u00f0urfr\u00e6\u00f0ideild H\u00e1sk\u00f3la \u00cdslands.\u00a0<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var Eir\u00edkur Steingr\u00edmsson pr\u00f3fessor. Auk hans s\u00e1tu \u00ed doktorsnefnd Gu\u00f0r\u00fan Valdimarsd\u00f3ttir d\u00f3sent, P\u00e9tur Henry Petersen pr\u00f3fessor og Lionel Larue, pr\u00f3fessor vi\u00f0 Institut Curie \u00ed Frakklandi.<\/p>\n

\u00de\u00f3rarinn Gu\u00f0j\u00f3nsson, pr\u00f3fessor, deildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.<\/p>\n

\u00c1grip<\/strong><\/p>\n

Litfrumur eru me\u00f0al frumuger\u00f0a sem eiga uppruna sinn \u00ed taugakambi snemma \u00ed \u00feroskun hryggd\u00fdra. Forverafrumur litfruma, sem nefnast melanoblast-frumur, myndast \u00ed taugakambi en fj\u00f6lga s\u00e9r \u00e1\u00f0ur en \u00fe\u00e6r fer\u00f0ast til a\u00f0 \u00feekja allt yfirbor\u00f0 h\u00fa\u00f0arinnar. \u00deessar frumur fara inn \u00ed \u00feekju h\u00fa\u00f0arinnar \u00e1\u00f0ur en hinar eiginlegu litfrumur ver\u00f0a til og hefja myndun litarefnis. \u00cd m\u00fasum enda flestar litfrumur \u00ed h\u00e1rsekknum \u00fear sem \u00fe\u00e6r flytja litarefni \u00ed h\u00e1ri\u00f0. \u00deetta fl\u00f3kna ferli kallar \u00e1 \u00fdmis stj\u00f3rnpr\u00f3tein og umritunar\u00fe\u00e6tti. Einn mikilv\u00e6gasti umritunar\u00fe\u00e1tturinn \u00ed litfrumum er MITF e\u00f0a Microphthalmia-associated Transcription Factor en hann er nau\u00f0synlegur fyrir frumufj\u00f6lgun, lifun og frumufar \u00ed myndun litfruma. Hlutverk Mitf hefur einkum veri\u00f0 rannsaka\u00f0 \u00ed sortu\u00e6xlisfrumum en \u00fe\u00f3tt \u00fe\u00e6r eigi uppruna sinn \u00ed litfrumum hafa frumurnar breyst vi\u00f0 \u00e6xlismyndunina og \u00fev\u00ed ekki lj\u00f3st a\u00f0 hi\u00f0 sama eigi vi\u00f0 \u00ed litfrumunum e\u00f0a forverum \u00feeirra. St\u00f6kkbreytingar \u00ed Mitf geni m\u00fasa lei\u00f0a oftast til \u00feess a\u00f0 litfrumurnar og forvera \u00feeirra vantar alveg og \u00fev\u00ed hefur reynst erfitt a\u00f0 skilgreina in vivo hlutverk gensins \u00ed hinum \u00fdmsu skrefum litfrumu\u00feroskunar.<\/p>\n

H\u00e9r er l\u00fdst skilyrtri st\u00f6kkbreytingu \u00ed Mitf geni m\u00fasar \u00fear sem t\u00e1knunum fyrir am\u00edn\u00f3s\u00fdru 243 er breytt \u00far l\u00fdsin \u00ed argin\u00edn. \u00deegar \u00feessi breyting var k\u00f6llu\u00f0 fram \u00ed litfrumum ur\u00f0u einungis til m\u00fds me\u00f0 mislit sv\u00e6\u00f0i \u00fear sem skiptust \u00e1 sv\u00f6rt, gr\u00e1 og hv\u00edt sv\u00e6\u00f0i. \u00der\u00e1tt fyrir MitfK243R st\u00f6kkbreytinguna hafa einhverjar starfh\u00e6far litfrumur or\u00f0i\u00f0 til (sv\u00f6rt sv\u00e6\u00f0i), einhverjar eru vanstarfh\u00e6far (gr\u00e1 sv\u00e6\u00f0i) og enn a\u00f0rar eru \u00f3starfh\u00e6far e\u00f0a vantar alveg (hv\u00edt sv\u00e6\u00f0i). Me\u00f0 \u00fev\u00ed a\u00f0 rekja litfrumurnar \u00ed \u00feroskun var s\u00fdnt a\u00f0 mun f\u00e6rri litfrumur ver\u00f0a til og \u00edfer\u00f0 \u00feeirra inn \u00ed \u00feekjuna gerist sjaldnar. Frumul\u00ednur voru \u00fatb\u00fanar \u00far litfrumum m\u00fasanna og nota\u00f0ar til a\u00f0 sko\u00f0a \u00e1hrif st\u00f6kkbreytingarinnar in vitro.\u00a0 Ni\u00f0urst\u00f6\u00f0urnar s\u00fdna a\u00f0 \u00feegar MitfK243R st\u00f6kkbreytingin er virkju\u00f0 \u00ed frumul\u00ednunum f\u00e6kkar frumuskiptingum og lifun frumanna minnkar. Ra\u00f0greining RNA sameinda s\u00fdndi a\u00f0 st\u00f6kkbreytingin hefur s\u00e9rt\u00e6k \u00e1hrif \u00e1 tj\u00e1ningu markgena og a\u00f0 \u00feau \u00e1hrif \u00fatsk\u00fdra a\u00f0 hluta \u00e1hrif st\u00f6kkbreytingarinnar \u00e1 \u00feroskun litfruma.<\/p>\n

Abstract<\/strong><\/p>\n

Establishment of melanocytes, the pigment-producing cells, starts from the multipotent neural crest cells. Melanoblasts, the melanocyte precursor cells, follow a tight schedule during their development requiring proliferation, migration, and invasion of the epidermis before they form the pigment producing melanocytes. In the mouse, most melanocytes localize to the hair bulb where they deliver melanin to the hair, which gives mice their coat color. As melanocyte development is complex, this process involves many regulatory proteins and transcription factors. Microphthalmia-associated Transcription Factor (Mitf) is required for proliferation, survival and migration during the formation of melanocytes, and has therefore been suggested as the key regulator of their development. The role of Mitf has been largely studied in melanoma cells, but little is known about its role in the generation of the melanocytes. In mice, mutations in Mitf lead in most cases to the absence of melanocytes, making it difficult to observe melanoblasts during the development in vivo. We have generated an inducible mutation in MITF in the mouse by changing lysine in position 243 into an arginine. We induced this mutation in melanocytes resulting in mice with alternating areas of black, grey and white areas. This means that despite the MitfK243R mutation, some melanocytes have grown, migrated and differentiated, while others did not (hypomorphic phenotype), displaying heterogeneity for the fate of melanocytes during development upon the MitfK243R mutation. We found that in these mice, fewer melanoblasts develop and they are not able to invade the epidermis to reach the hair follicle. We generated melanocyte primary cell lines from the mice and used those to perform in vitro studies. The results revealed that upon activation of the MitfK243R mutation, the cells exhibited reduced proliferation and survival. RNAseq analysis revealed genes that are differentially regulated by MITF upon induction of the MitfK243R mutation that might explain how this conditional mutation dysregulates the development of melanocytes.\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Romain Maurice Jacques Lasseur er f\u00e6ddur \u00e1ri\u00f0 1993 \u00ed Viriat \u00ed Frakklandi. Hann lauk BS-gr\u00e1\u00f0u fr\u00e1 h\u00e1sk\u00f3lanum Claude Bernard Lyon 1 \u00ed Frakklandi \u00e1ri\u00f0 2015 og MS-gr\u00e1\u00f0u fr\u00e1 Aix-Marseille h\u00e1sk\u00f3lanum \u00e1ri\u00f0 2017. Romain h\u00f3f doktorsn\u00e1m \u00ed n\u00f3vember 2018. Hann vinnur n\u00fa a\u00f0 ranns\u00f3knum s\u00ednum \u00e1 ranns\u00f3knarstofu Eir\u00edks Steingr\u00edmssonar vi\u00f0 L\u00e6knadeild Heilbrig\u00f0isv\u00edsindasvi\u00f0s H\u00e1sk\u00f3la \u00cdslands. Romain er kv\u00e6ntur Mathilde Garaboux og eiga \u00feau tv\u00f6 b\u00f6rn, Lyru Margaux Heklu og Nino Cahir \u00de\u00f3r.<\/p>\n<\/div><\/div>","protected":false},"featured_media":5685,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2024-06-18T13:00:00+00:00","_phd_date_end":"2024-06-18T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"\u00c1hrif skilyrtrar st\u00f6kkbreytingar \u00ed Mitf geni m\u00fasar \u00e1 \u00feroskun og starfsemi litfruma. 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