Target validation.

Slides:

Advertisements

Similar presentations

Clinical Group n Biology of HIV infection n by Duangrat Inthorn n Mechanism of Reverse Transcriptase Inhibitors and Protease Inhibitors n by Tawitch Suriyo.

Advertisements

The future of technology, law enforcement, and justice ICJIA Feburary, 2013.

THE REPLICATION OF VIRUSES Virology Lecture 2 Three lectures dealing with (1) replication of DNA viruses (2) the culture, growth and recognition of virus.

Viruses.  What is a virus? Defined by their inability to replicate/multiply without utilizing a host cells reproductive mechanisms. Only contain ONE.

HIV Replication Rachel Carriger Biochemistry Fall 2004.

HIV and AIDS Human Immunodeficiency Virus (HIV) is the virus that causes Acquired Immunodeficiency Syndrome (AIDS).

Introduction to Computers QUME Some objectives  define the term, computer, and discuss four basic computer operations  understand the terms hardware.

Vaccines and Antivirals. Clinical Use of Interferon Therefore they have been used in the treatment of cancers of various types. Therefore they have been.

11/27/2001Database Management -- R. Larson Databases and the Future (Cont.) University of California, Berkeley School of Information Management and Systems.

TECH-A KUCHA 4th. June Do You Know… Who Owns the Internet? No one actually Organizations that oversee and standardize what happens on the Internet.

HIV and AIDS Retrovirus -> Primate Lentivirus Group.

HIV Structure, Lifecycle, and Replication

 Virus = an infectious particle consisting of nucleic acid enclosed in a protein coat and, in some cases, a membranous envelope  NOT living (unable.

Trends in Biotechnology TB 14 Microinjection, stem cell transfer, gene targeting, and use of retroviruses 1.

Transfection. What is transfection? Broadly defined, transfection is the process of artificially introducing nucleic acids (DNA or RNA) into cells, utilizing.

Antibodies I’ve heard of them but just what are they? Plasma Cells of Effector Cells Transcription Translation Polypeptide / Proteins Humoral Response:

Viruses Chapter 19. A Borrowed Life Virus: an infections particle incapable of replicating outside of a cell, which consists of an RNA or DNA genome enclosed.

Product Strategy New Products and Life Cycles. Memorable Product Forecasts “640K ought to be enough for anybody.” - Bill Gates, 1981 “We don’t like their.

1 AIDS Acquired immune deficiency syndrome A group of illnesses resulting from immune system damage caused by infection with HIV.

Viruses. Biology of Viruses Structure of Viruses: Size -Less then 0.2 microns Parts of the Virus 1)Capsid: -Made of protein subunits 2) Inner core: made.

HIV molecular biology BTY328: Virology

Modeling in Computer Architecture Matthew Jacob. Architecture Evaluation Challenges Skadron, Martonosi, August, Hill, Lilja and Pai, IEEE Computer, Aug.

Computers in Education Past, Present, and Future

Control of Gene Expression. Ways to study protein function by manipulating gene expression Mutations –Naturally occurring, including human and animal.

Putting Things in Perspective: Selective Quotes. “640K ought to be enough for anyone.” Bill Gates, 1981.

"I think there is a world market for maybe five computers." --Thomas Watson, chairman of IBM, 1943.

The Digital Distribution of Media: The Opportunity.

JAMM 1001 New Technology, Part 1 Computers + Communication = The Internet.

A History of Computers. 500 BC: The abacus Not a whole lot… The Roman Empire, Jesus, King Arthur, the Dark Ages, The Renaissance, Christopher Colombus,

MD 815 Session #3 Technology Forecasting 1. Introduction 2. Quantitative forecasting techniques 3. Predicting Diffusion Case.

Introduction to Viruses. Viruses are ‘disease causing agents’. Nucleic Acid surrounded by a protein coat called a capsid Some have a additional external.

VIRAL STRUCTURE Image source: healthoma.com. Sources: raritanval.edu; slavirusportfolio.wikispaces.com, virology.wisc.edu.

Basics of HIV Virus Vijay Kandula, MD MPH AAHIVS

19.09 Replication of HIV Slide number: 1

Good teaching is more a giving of right questions than a giving of right answers. – Josef Albers Viruses Chapter 19.

Viruses Page 328.

CHAPTER 12 THE STRUCTURE AND INFECTION CYCLE OF VIRUSES

A-LEVEL BIOLOGY RNA interference (RNAi)

Plate 32 Viral Replication.

Human Immunodeficiency Virus (HIV) Acquired Immuno Deficiency Syndrome (AIDS)

Immunodeficiency (2 of 2)

VIRUSES Viruses – are segments of nucleic acids contained in a protein coat; they are not cells; they are smaller than prokaryotes and range in size.

Viruses Chapter 19 Page 478.

A typical enveloped virus

Structure of a virus All viruses have a protein coat that surrounds nucleic acid. The nucleic acid may be DNA or RNA.

More opinions may be necessary!

General Animal Biology

Viruses Viruses – are segments of nucleic acids

Chapter 15 Viruses, Viral Life Cycles, Retroviruses.

mRNA Degradation and Translation Control

Other biological particles

Immunodeficiency (2 of 2)

Unit 2 – Biodiversity - Virus

Emerging technologies

Antiviral RNA-induced silencing complexes

Protein interactions during the flavivirus life cycle elucidated by MS-based proteomics. Protein interactions during the flavivirus life cycle elucidated.

Volume 134, Issue 4, Pages (August 2008)

VIRUSES Viruses – are segments of nucleic acids contained in a protein coat; they are not cells; they are smaller than prokaryotes and range in size.

Good teaching is more a giving of right questions than a giving of right answers. – Josef Albers Viruses Chapter 19.

Viruses Page 328.

Terminology HIV AIDS Acquired Human Immune Immunodeficiency Deficiency

Viruses Page 328.

VIRUSES Viruses – are segments of nucleic acids contained in a protein coat; they are not cells; they are smaller than prokaryotes and range in size.

Unit 2: Organisms and Evolution Advanced Higher Biology Miss Aitken

This “telephone” has too many shortcomings to be seriously considered as a means of communication. The device is inherently of no value to us. Western.

Presentation transcript:

Target validation

Target validation

Target Validation—Overview Knock-out/Knock-in/Gain-of-function, Transgenic Models Pathways (Examples include the drugs acting on the cholesterol synthesis pathway) Clinical Data Antisense DNA/RNA and RNAi Chemical Knock-out and Chemical Biology

Target Validation Methods: Pre-genomic

Target validation Wann ist ein target für therapeutische Zwecke tauglich, also valid ? Wenn es in hinreichend kausalem Zusammenhang mit der Krankheit steht: Als Enzym, GPCR, Ionenkanal, Rezeptor usw. Überprüfung durch screening mit Leitstrukturen aus focused libraries Als target auf DNA, RNA, mRNA Ebene selber Überprüfung durch knockout Mutationen (siehe unten), single point Mutationen (SNPs, siehe unten), und gene silencing mittels durch RNA interference (RNAi) (siehe siRNA)

Target validation

Target validation

Target validation

Human Immunodeficiency Virus(HIV) Human Immunodeficiency Virus(HIV). The outer shell of the virus is known as the Viral enevlope. Embedded in the viral envelope is a complex protein known as env which consists of an outer protruding cap glycoprotein (gp) 120, and a stem gp 41. Within the viral envelope is an HIV protein called p17 (matrix), and within this is the viral core or capsid, which is made of another viral protein p24 (core antigen).

STRUCTURE OF HIV-1 VIRUS envelope glycoproteins dřeňové proteiny Gp120 (cap) Gp41 (Stem) P17(matrix) P24 capsid(core antigen) core proteins p9 lipidic bilayer p32 reverse transkriptase (p66) RNA

Target validation

Target validation

HIV-1 HOST CELL INTERACTION IST initiation IIND adsorption IIIRD penetration gp41 gp120 gp41 binding- site for CD4 molecule viral RNA gp120 V3loop V1 V3 V3loop V2 CCR5 CD4 V3 CD4 CCR-5 V4

Target validation

Target validation

Prediction is very difficult, especially about the future (Niels Bohr, also attributed to Mark Twain) "Everything that can be invented has been invented." Charles H. Duell, U.S. Office of Patents, 1899. "I think there is a world market for maybe five computers." Thomas Watson, Chairman IBM, 1943 "Computers in the future may weigh no more than 1.5 tons." Popular Mechanics, forecasting the relentless march of science, 1949 "There is no reason anyone would want a computer in their home." Ken Olson, President, Chairman and Founder of Digital Equipment Corp., 1977 "640 k ought to be enough for anybody." Bill Gates, Founder of Microsoft, 1981

Important Mispredictions in Drug Therapy There is no market for cyclosporin, because there are too few organ transplants. The breakthrough in transplantation medicine was enabled by cyclosporin. There is no market for Cimetidin. Gastric and duodenal ulcera can be treated conventionelly (by surgery!) In 1983, six years after its market introduction, cimetidin had yearly sales of one billion US-$. Omeprazole will „dry out“ the stomach, because of its complete blockade of gastric acid production. Omeprazole developed to the most successful drug of all time (more than six billions US-$/year).