Aquatic Biotechnology

1
Chapter 10

• Aquatic Biotechnology

2
Aquatic Biotechnology

• Increasing the worlds food supply
• Improving seafood safety and quality
• Identifying novel compounds for the benefit of
  human health and medical treatments
• Seeking new approaches to monitor and treat
  disease
• Bioprocessing
• Restoring and protecting marine ecosystems

3
Chapter 11

• Medical Biotechnology

4
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

5
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

6
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 Gehrigs,
  Huntingtons, Parkinsons

7
Detecting and Diagnosing Human Disease Conditions

• Models of Human Disease
• Heart attack mice
• Defect in cholesterol uptake

8
Detecting and Diagnosing Human Disease Conditions

• Detecting Genetic Diseases

9
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)

10
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

11
Detecting and Diagnosing Human Disease Conditions

• Detecting Genetic Diseases
• Testing for chromosome abnormalities and
  defective genes
• RFLP (restriction fragment length polymorphisms)

12
Detecting and Diagnosing Human Disease Conditions

• Detecting Genetic Diseases
• Testing for chromosome abnormalities and
  defective genes
• ASO allele-specific oligonucleotide analysis

13
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 gt 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

14
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 patients DNA to a gene sequence on
  the chip indicates that the persons DNA has a
  particular mutation or SNP

15
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

16
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
17
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

18
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!)

19
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

20
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

21
Medical Products and Applications of Biotechnology

• Artificial Blood
• Started testing of blood in 1980s 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?

22
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 Alzheimers disease or drug
  addiction
• Using antibodies in some types of therapies
  Development of Monoclonal Antibodies

23
Gene Therapy

• How is it done?

24
Gene Therapy

• How is it done?
• Delivering the payload viral vectors for gene
  delivery

25
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 cant move chloride out, they absorb
  water trying to dilute the chloride in the cell
• This leads to the production of THICK sticky
  mucus

26
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
27
Regenerative Medicine

• Growing cells and tissues that can be used to
  replace or repair defective tissues and organs

28
Regenerative Medicine

• Cells and Tissue Transplantation
• 50,000 Americans are diagnosed with Parkinsons
  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

29
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

30
Regenerative Medicine

• Cells and Tissue Transplantation
• Organ transplantation
• 8 million surgeries are performed each year and
  about 4000 people die waiting
• Autograft transplanting a patients 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 - gt70 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.

31
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

32
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

33
Regenerative Medicine

• Tissue Engineering
• Replacement of tissues and organs by growing them
  in culture
• So far skin grafts have been successfully
  engineered

34
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
  laces-prevents unraveling)
• A cells 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

35
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!
36
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!

37
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

38
Regenerative Medicine

• Stem Cell Technologies
• Potential Applications of Stem Cells

39
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?

40
Regenerative Medicine

• Cloning
• Therapeutic Cloning and Reproductive Cloning

41
Human Genome Project

• How was this done?

42
Human Genome Project

• Revealed disease genes on all human chromosomes