Scientists need to earn the trust and confidence
- Slides: 47
Scientists need to earn the trust and confidence of the public if we are to retain our “license to operate. ” But to do that we have to be accurate about what science can do. It is no good exaggerating what science can deliver, as happened when the Director of the National Cancer Institute, Dr. Andrew von Eschenbach, announced the Institute’s challenge goal in 2003 as “To eliminate the suffering and death due to cancer by 2015. ” This cannot be justified even as a statement of aspiration because when we fail to deliver, as we surely will with such a claim, we will lose the confidence and trust of both the politicians and the public. Paul M. Nurse
CDC 28 kóduje p 34! „cyclin-dependent kinase“, CDK
Transkripční (pretranslační? ) regulace v buněčném cyklu
Cykliny jsou spřízněné s TFIIB a p. Rb! Nucleic Acids Res. 1994 March 25; 22(6): 946– 952.
Co dělají „příbuzní“ cyklinů? viz též Pho 80/85
Cykliny jakožto derivát transkripčních regulátorů? A co CDK? ? (Noble et al. 1997)
CDK-like kinázy a transkripce • TFIIH • CTD kinase (S. cer. : KIN 28) • P-TEFb (Positive. Transcription Elongation Factor). . . + cyclin T (referát)
Guo and Stiller 2004 RNA proc. ? G 2 M? P-TEFb 16 Arabidopsis CDK dosud zmeškáno, 2 CDK 10/11 a 14 recentně duplik. CDK 9 Cdk. C Cdk. B Cdk. A Cdk. F CAK + TFIIH CTD kinase Cdk. D Cdk. E
„Pocket proteins“ - příbuzenstvo cyklinů: p. RB a spol.
p. RB a E 2 F – regulace „S-fázních efektorů“
Mechanismus represe je možná trochu složitější. . . Rb indukuje deacetylaci histonů, což brání transkripci přísluš. oblasti chromatinu
Další efektory p. Rb Korenjak and Brehm 2005
. . . a není to živočišná specialita! GSH DNA damage
Regulace transkripce se uplatňuje i jinde v BC.
Je transkripce tak důležitá, nebo o ní jen hodně víme? • Měření množství m. RNA: – Northern – Microarrays • Měření produkce m. RNA je něco jiného!! A jak se vůbec transkripce dá regulovat?
Microarrays
Kvasinkový BC jakožto posloupnost „vln“ cyklinů
Yang a Kornbluth, Ti. BS 1999 Důvody ale nejsou pouze transkripční!
jádro cytoplasma koncentrace/aktivita Cykliny: A, E, D 1, B 2 G 1 S G 2 M
Transkripční regulace v BC S. cerevisiae Gene expression during the yeast cell cycle. Genes correspond to the rows, and the time points of each experiment are the columns. The ratio of induction/repression is shown for each gene such that the magnitude is indicated by the intensity of the colors displayed. If the color is black, then the ratio of control to experimental c. DNA is equal to 1, whereas the brightest colors (red and green) represent a ratio of 2. 8: 1. Ratios >2. 8 are displayed as the brightest color. In all cases red indicates an increase in m. RNA abundance, whereas green indicates a decrease in abundance. Gray areas (when visible) indicate absent data or data of low quality. Color bars on the right indicate the phase group to which a gene belongs (M/G 1, yellow; G 1, green; S, purple; G 2, red; M, orange). These same colors indicate cell cycle phase along the top. (A) Gene expression patterns for cell cycle-regulated genes. The 800 genes are ordered by the times at which they reach peak expression. Spellman et al. 1998
Mechanismy regulace: historický „krok stranou“ - přepínání párovacích typů pučivé kvasinky a/ 2 a + 2 Párovací typ určen jediným lokusem, ale HOMOTHALISMUS!!!
Kazetový model MAT lokusu - konverzi zahajuje HO endonukleáza
Transkripční regulace HO • • Jen v haploidech Jen v mateřských buňkách Jen v G 1 (booleovské AND) Nástroj ke studiu: swi (switching) mutanti
Promotor genu HO M/D specifita Swi 5? diploid-specif. G 1 specifita Swi 4/6
Swi 5 a asymetrie M/D D 1 D 2 D 1 M M D 2 a Swi 5 podmínkou M exprese HO (ale nikoli důvodem asymetrie!)
Swi 5 na URS 2 SWI 5 m. RNA Regulovaná lokalizace Swi 5 p G 1 S G 2 (přetrvávající Swi 5 v M? ? ? ) M
Regulace jaderné lokalizace Swi 5 p • S/G 2/M - P ace • M/G 1 - de P ace • fosforylace závisí na Cdc 28! • defosforylace: Cdc 14 NLS
(Jak je to s tou M/D asymetrií? ) G 1 jádro aktin Myo 4/She 2/3 Ash 1 m. RNA ASH 1: asymmetry of HO switching - D-specif. represor!
Lokalizace m. RNA jakožto univerzální způsob vzniku asymetrie?
A co G 1 specifická regulace? • Swi 4/Swi 6 váží SCB (Swi Cell Cycle Box) • SCB = CACGAAAA – např. v promotorech CLN 1, CLN 2! – SWI 4/6 = SBF = SCB Binding Facror • MCB = Mlu. I Cell Cycle Box = ACGCGTNA • MBF (MCB Binding factor) = Swi 6 + Mbp 1 Historie Mbp 1 - „Emily factor“
Transkripční faktory rodiny Swi 4/Swi 6
I tyto proteiny podléhají fosforylaci. . .
(Lehce diskutabilní) funkční překryvy. . . (Bean et al. 2005)
G 1 -specifická exprese (pro Pho 85)
Další BC-regulované geny S. cer. + histony! + Fkh 1/2!
Příklad transkripčně regulovaných „efektorů“: separace buněk ACE 2: • homolog Swi 5, podobně regulován • reguluje mj. chitinázu!
Kvasinka znovu – skupiny kotranskrib. genů
Lze identifikovat regulační obvody?
Paradox regulace HO: je „start“ transkripční událost? START SWI 4/6 CLN 1, 2 velikost CLN 3 HO START SWI 4/6 CLN 1, 2
Co se stane, když buňka nemá CLB? Amon et al. 1993
Nelze vypnout CLN! CLN 2/CDC 28 m. RNA ratio
CLN regulují expresi CLB Amon et al. 1993
X: proteiny rodiny Forkhead (Fkh 1, Fkh 2)
(CDK inhibitor; viz příště!! Jorgensen and Tyers 2000
- How to get your parents trust back
- Confidence interval vs confidence level
- Confidence interval z value
- Cipd case law
- Is worthy a scam
- Trust faith or confidence in someone or something
- Charitable work
- Ap world leq conclusion
- 7elife com
- Paycheck
- Rhyme with earn
- Fasten 2. hali
- Iousa worksheet
- The terrible storm could be a symbol for
- In a video game you earn 5 points for each jewel
- Frances louisa tracy
- Fm group fragrance
- What is bac project management
- How much does wanda earn per hour
- Earn ebly
- Victoria velkova
- Mary jane is a lawyer who can earn
- After the experiment scientists organize and the data
- Diagrams tables and graphs are used by scientists mainly to
- Hình ảnh bộ gõ cơ thể búng tay
- Lp html
- Bổ thể
- Tỉ lệ cơ thể trẻ em
- Gấu đi như thế nào
- Tư thế worm breton là gì
- Bài hát chúa yêu trần thế alleluia
- Các môn thể thao bắt đầu bằng tiếng đua
- Thế nào là hệ số cao nhất
- Các châu lục và đại dương trên thế giới
- Công thức tính thế năng
- Trời xanh đây là của chúng ta thể thơ
- Mật thư tọa độ 5x5
- 101012 bằng
- Phản ứng thế ankan
- Các châu lục và đại dương trên thế giới
- Thơ thất ngôn tứ tuyệt đường luật
- Quá trình desamine hóa có thể tạo ra
- Một số thể thơ truyền thống
- Cái miệng xinh xinh thế chỉ nói điều hay thôi
- Vẽ hình chiếu vuông góc của vật thể sau
- Nguyên nhân của sự mỏi cơ sinh 8
- đặc điểm cơ thể của người tối cổ
- Ví dụ giọng cùng tên