Новое семейство генов иммунной системы млекопитающих, имеющих лизоцим-подобный домен, и их потенциальная применимость для генной терапии рака тема диссертации и автореферата по ВАК РФ 03.00.26, доктор биологических наук Киселев, Сергей Львович
Киселев, Сергей Львович
доктор биологических наук
2000
- Специальность ВАК РФ03.00.26
- Количество страниц 224
Заключение диссертации по теме «Молекулярная генетика», Киселев, Сергей Львович
выводы
1. Впервые клонирован новый ген мыши tag7. Определена первичная структура, регуляция, локализация. Показано, что ген участвует в функционировании иммунной системы организма. Продемонстрировано, что белок Тад7 является секреторным, индуцибельным, формирует мультимерные комплексы in vivo и может индуцировать апоптоз.
2. Клонирован человеческий гомолог гена tag7, показана высокая гомология и консервативность мышиного и человеческих генов. Показано, что экспрессия гена не ассоциирована с опухолевыми процессами.
3. Обнаружен и клонирован ген млекопитающих, tagL, имеющий гомологию с геном tag7 в районе лизоцим-подобного домена. Определена его структура, показан характер его экспрессии, секреции и индукции клетками иммунной системы.
4. Продемонстрировано, что гены tag7 и tagL млекопитающих являются представителями нового семейства генов эукариот, участвующих в иммунной защите организма.
5. Впервые показано, что модификация опухолевых клеток геном tag7 приводит к значительному ингибированию роста опухоли, за счет опосредованной индукции апоптоза клеток опухоли и не связана с Т клеточным ответом организма.
6. Впервые разработана противоопухолевая клеточная вакцина на основе аутологичных опухолевых клеток, модифицированных геном tag7. Показана ее эффективность в сравнении с клетками
БЛАГОДАРНОСТИ
Автор выражает свою глубокую признательность и благодарность своим научным консультантам академику Георгиеву Георгию Павловичу и член-корреспонденту Гнучеву Николай Васильевичу за участие, которое они приняли в проведении исследований и подготовке материалов диссертационной работы. Ученому секретарю ИБГ РАН Грабовской Любови Сергеевне и заместителю директора Садчиковой Елене Рубеновне за внимание и помощь. Особую благодарность выражает сотрудникам отдела Молекулярной генетики рака: Коробко Алене, Миркиной Ирине, Кибардину Алексею, Ларину Сергею, Кустиковой Ольге за неоценимый вклад в выполнение представленной работы, Сащенко Лидии Павловне, Коробко Игорю, Захаровой Елене, Ивановой Тамаре за постоянную помощь, советы и поддержку. Отделу снабжения ИБГ РАН, во главе со Светланой Сергеевной Волковской, за прекрасное обеспечение необходимыми материалами. Всем сотрудникам ИБГ РАН за то участие, которое они принимали в представленной работе.
Сотрудникам ИБХ РАН Габибову Александру Габибовичу, Суровому Андрею Юрьевичу и Лагарьковой Марии (МГУ) за помощь, советы и поддержку.
Брызгалову И. (РОНЦ РАМН) за помощь в проведении экспериментов на животных, Райхлину Натан Танфелеевичу (РОНЦ РАМН) за неоценимую помощь в проведении гистологических и электронно-микроскопических исследований. Барышникову А.Ю и Козлову АМ (РОНЦ РАМН) за помощь в составлении Протокола клинических испытаний.
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