Transcript Chapter 10 and 11

Chapter 10
Aquatic Biotechnology
Aquatic Biotechnology
z Increasing the world’s food supply
z Improving seafood safety and quality
z Identifying novel compounds for the benefit
of human health and medical treatments
z Seeking new approaches to monitor and
treat disease
z Bioprocessing
z Restoring and protecting marine ecosystems
Chapter 11
Medical Biotechnology
Detecting and Diagnosing
Human Disease Conditions
Models of Human Disease
• Identify diseases and test therapies before clinical
trials in humans
• Clinical trials: three phases
• Phase I: safety studies- safe dose and how to administer the
dose (ADME)
• Phase II: few hundred patients for the purpose of testing
effectiveness
• Phase III: effectiveness compared to other drugs –involve
thousands of patients often with different backgrounds and
stages of illness throughout the country
Detecting and Diagnosing
Human Disease Conditions
Models of Human Disease
• Rat gene, ob, also found in humans therefore
homologous
• Codes for a protein hormone called leptin if
missing leads to obesity
• Found that treating obese children defected in this
gene with leptin decreases their weight
Detecting and Diagnosing
Human Disease Conditions
Models of Human Disease
• Organism has 959 cells, 131 of them are destined to
go through apoptosis
• Study programmed cell death in this organism
• Programmed cell death important to correct development of
the fetus and improper cell death is implicated in:
Alzheimers, Lou Gehrig’s, Huntington’s, Parkinson’s
Detecting and Diagnosing
Human Disease Conditions
Models of Human Disease
• Heart attack mice
• Defect in cholesterol uptake
Detecting and Diagnosing
Human Disease Conditions
Detecting Genetic Diseases
Detecting and Diagnosing
Human Disease Conditions
Detecting Genetic Diseases
• Testing for chromosome abnormalities and defective genes
• Amniocentesis (Test at 16 weeks - karyotype)
• Chorionic villus sampling (Test at 8 to 10 weeks - karyotype)
Detecting and Diagnosing
Human Disease Conditions
Detecting Genetic Diseases
• Testing for chromosome abnormalities and defective genes
• Fluorescence in situ hybridization (FISH)
• Fluorescence probes that are specific for chromosomes and/or genes
• Spectral karotype
Detecting and Diagnosing
Human Disease Conditions
Detecting Genetic Diseases
• Testing for chromosome abnormalities and defective genes
• RFLP (restriction fragment length polymorphisms)
Detecting and Diagnosing
Human Disease Conditions
Detecting Genetic Diseases
• Testing for chromosome abnormalities and defective genes
• ASO allele-specific oligonucleotide analysis
Detecting and Diagnosing
Human Disease Conditions
 Detecting Genetic Diseases
• Single Nucleotide Polymorphisms (SNPs)
• One of the most common forms of genetic variation
• Estimated that one SNP occurs approximately every 1,000-3,000 bp in the
human genome
• 99.9 percent of the DNA sequence will be exactly the same –> 80% of 0.1
percent variation will be SNPs
• Most have no effect because they occur in non-protein coding regions
(introns)
• 10 pharmaceuticals donated millions in a collaborative partnership called
the SNP Consortium
Detecting and Diagnosing
Human Disease Conditions
Detecting Genetic Diseases
• Identifying sets of disease
genes by microarray analysis
• Microarray created with known
diseased genes or SNPs
• DNA from a patient is tagged
with fluorescent dyes and then
hybridized to the chip
• Binding of a patient’s DNA to a
gene sequence on the chip
indicates that the person’s DNA
has a particular mutation or
SNP
Detecting and Diagnosing
Human Disease Conditions
Detecting Genetic Diseases
• Protein Arrays
• Chips contain antibodies
• Apply blood from a patient
• Proteins from disease-causing organisms can be detected
Medical Products and
Applications of Biotechnology
The search for new medicines and drugs
• Pharmacogenomics
• Different individuals with the same disease often respond
differently to a drug treatment because of differences in gene
expression.
Animation
Medical Products and
Applications of Biotechnology
The search for new medicines and drugs
• Oncogenes- genes that produce proteins that may function
as transcription factors and receptors for hormones and
growth factors, as well as serve as enzymes involved in a
wide variety of ways to change growth properties of cells
that cause cancer
• Tumor Suppressor Genes – regulate oncogenes
Medical Products and
Applications of Biotechnology
The search for new medicines and drugs
• Personalized Medicine
• BRCA1 or 2 – increases risk of developing breast cancer
• But there are many other cases of breast cancer that do not exhibit
this mode of inheritance
• They SHOULD be treated differently (i.e. different chemotherapy!)
Medical Products and
Applications of Biotechnology
The search for new medicines and drugs
• Improving techniques for drug delivery
• Factors that influence drug effectiveness
• Drug solubility
• Drug breakdown
• Drug elimination
• Microspheres – tiny particles that can be filled with
drugs
Medical Products and
Applications of Biotechnology
The search for new medicines and drugs
• Nanotechnology and Nanomedicine
• nanosensors that can monitor blood pressure, hormone
concentrations, unblock arteries, detect and eliminate cancer cells
Medical Products and
Applications of Biotechnology
Artificial Blood
• Started testing of blood in 1980’s for HIV
• However it is still not tested in poor, developing countries
• There is a need for safe-blood
• Possibilities: cell free solutions containing molecules that
can bind to and transport oxygen; or blood substitutes
such as Hemopure that is made from the hemoglobin of
cattle
• What does blood matching mean?
Medical Products and
Applications of Biotechnology
Vaccines and Therapeutic Antibodies
• Vaccines stimulate immune system
• Also hope that vaccination may be useful against
conditions such as Alzheimer’s disease or drug addiction
• Using antibodies in some types of therapies: Development
of Monoclonal Antibodies
Gene Therapy
How is it done?
Gene Therapy
How is it done?
•
Delivering the payload: viral vectors for gene delivery
Gene Therapy
 Targets for Gene Therapy
•
Treating cystic fibrosis
• Defective cystic fibrosis
transmembrane
conductance regulator
(CFTR)
• Normally it serves as a
pump at the cell membrane
to move electrically charged
chloride atoms out of the
cells
• If cells can’t move chloride
out, they absorb water
trying to dilute the chloride
in the cell
• This leads to the production
of THICK sticky mucus
Gene Therapy
Challenges Facing Gene Therapy
• Reaction to the vector, an adenovirus, led to the
death of Jesse Gelsinger
• It raised more questions than answers:
• Can gene expression be controlled in the patient?
• How long will the therapy last?
• What is the best vector?
Animation
Regenerative Medicine
Growing cells and tissues that can be used to
replace or repair defective tissues and organs
Regenerative Medicine
Cells and Tissue Transplantation
• 50,000 Americans are diagnosed with Parkinson’s annually
• Caused by a loss of dopamine-producing cells deep inside the brain
• Leads to tremors, weakness, poor balance, loss of dexterity,
muscle rigidity, reduced sense of smell, inability to swallow and
speech problems
• After 4 to 10 years the drugs become ineffective leading to a poor
quality of life for the patient
Regenerative Medicine
Cells and Tissue Transplantation
• Fetal tissue grafts
• The basic idea is to introduce fetal neurons which can establish
connection with other neurons
• Over 100 patients have received such transplants-shown some
recovery
Regenerative Medicine
Cells and Tissue Transplantation
• Organ transplantation
• 8 million surgeries are performed each year and about 4000 people
die waiting
• Autograft – transplanting a patient’s own tissue from one region of the
body to another- ex. Vein from leg used in coronary bypass-organ
transplants are between individuals and so must be checked for
compatibility
• Histocompatibility complex - >70 genes which produce tissue
typing proteins (must match!)
• There are many different types of MHC proteins (one group is
called human leukocyte antigens or HLAs)- have been using
immunosuppressive drugs but there are problems.
Regenerative Medicine
Cells and Tissue Transplantation
• Organ transplantation
• Xenotransplantation – transfer between species (pig to human)
• University of Missouri scientists have produced cloned, knockout pigs
that lack a gene called GGTA1 (or 1,3 galactosyltransferase)
• The gene normally codes for a sugar that would be recognized as
foreign by humans
Regenerative Medicine
Cells and Tissue Transplantation
• Cellular therapeutics
• Involves using cells to replace defective tissues to deliver important
biological molecules
• Encapsulate living cells into tiny plastic beads (biocapsules)
• Capsule protects the cells from rejection but yet allows chemicals
to diffuse out
• Could be used in Type 1 diabetes therapy
Regenerative Medicine
Tissue Engineering
• Replacement of tissues
and organs by growing
them in culture
• So far skin grafts have
been successfully
engineered
Regenerative Medicine
 Tissue Engineering
• The telomere story
• Usually 8 to 12,000 base pair units of the the repeating sequence 5’TTAGGG-3’. (think of plastic tabs at the end of your shoe lacesprevents unraveling)
• A cell’s lifespan is affected in part by telomeres –each time a cell
divides, telomeres shorten slightly-which leads to senescence! (aged
cells!)
• Telomerase repairs telomere length by adding DNA nucleotides to cap
the telomere after each round of cell division
Regenerative Medicine
Stem Cell Technologies
• The CDC estimates hat
3,000 Americans die
every day from diseases
that may one day
potentially be treated by
stem cell technologies
• What are stem cells?
Known as
Pluripotent!
Regenerative Medicine
Stem Cell Technologies
• What are stem cells?
• Two major properties:
• ES cells can self-renew indefinitely to produce more stem cells
• Under the proper growth conditions, ES cells can differentiate into
a variety of mature cells with specialized functions
• Human ES cells avoid senescene in part because they express
high levels of telomerase!
Regenerative Medicine
Stem Cell Technologies
• Adult-derived stem cells do everything embryonic stem
cells can do and remove the ethical issue of destroying
embryos.
• Amniotic-fluid derived stem cells
• Reprogramming somatic cells
Regenerative Medicine
Stem Cell Technologies
• Potential Applications of Stem Cells
Regenerative Medicine
Stem Cell Technologies
• Questions that need to be answered:
• Is there an “ultimate” adult stem cell that could turn into every
tissue in the body?
• Why do stem cells self-renew and maintain an undifferentiated
state?
• What factors trigger division of stem cells?
• What are the growth signals (chemical, genetic, environmental)
that influence the differentiation of stem cells?
• What factors affect the integration of new tissues and cells into
existing organs?
Regenerative Medicine
Cloning
• Therapeutic Cloning and Reproductive Cloning
Human Genome Project
How was this done?
Human Genome Project
Revealed disease genes on all human chromosomes