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Wim Van Criekinge
Antwerpen
24 oktober 2013
Lab for Bioinformatics and computational genomics

Overview
^[now][transl⎮comput]ational[epi]genomic$

•
•
•
•

Who ? Wher...
biobix
wvcrieki

biobix.be
bioinformatics.be

3
EUKARYOTES

PROKARYOTES

All organisms: 1 or more cells
Lab for Bioinformatics and computational genomics

Cell Theory
• All organisms are
composed of one or
more cells.
• Cells ...
Each human cell contains 46 chromosomes (except sperm or egg cells)
Lab for Bioinformatics and computational genomics

Genetic code
DNA
Lab for Bioinformatics and computational genomics
Lab for Bioinformatics and computational genomics

DNA: Structure and Function
The human genome comprises the information ...
Lab for Bioinformatics and computational genomics

DNA: Structure and Function
The human genome comprises the information ...
Lab for Bioinformatics and computational genomics

DNA: Structure and Function
The human genome comprises the information ...
Genetic information is stored in the DNA
DNA encodes proteins
“Genes” encode proteins
DNA replication
DNA synthesis and proofreading
Mutations:
possible cause of diseases and disfunctionalities
Lab for Bioinformatics and computational genomics

Overview
^[now][transl⎮comput]ational[epi]genomic$

•
•
•
•

Who ? Wher...
Microbes are all over us
There are millions of microbes per
square inch on your body
Thousands of different species on the...
Lab for Bioinformatics and computational genomics

Defining Epigenetics
Genome
DNA

• Reversible changes in gene
expressio...
Lab for Bioinformatics and computational genomics

Chromatin is a Key Component of Epigenetic Mechanisms
Lab for Bioinformatics and computational genomics

Chromatin is a Key Component of Epigenetic Mechanisms
Cellular DNA is p...
Lab for Bioinformatics and computational genomics

Basic Epigenetic Mechanisms:
Post Translational Modifications to Histon...
Lab for Bioinformatics and computational genomics

Epigenetic Changes can Alter Chromatin Structure and Regulate Gene Expr...
Lab for Bioinformatics and computational genomics
Actionable
Epigenome
Lab for Bioinformatics and computational genomics

Epigenetics

• Epigenetics is essentially the
study of how our environm...
Lab for Bioinformatics and computational genomics

Epigenetic (meta)information = stem cells
Lab for Bioinformatics and computational genomics

Translational Research towards Personalised Medicine
•

•

DNA diagnost...
Lab for Bioinformatics and computational genomics

Historically, Cancer Was Considered
to be Driven Mostly by Genetic Chan...
Lab for Bioinformatics and computational genomics

Recent Evidence Shows that Epigenetic Changes are Also Important in Cau...
Lab for Bioinformatics and computational genomics

Biology uses methylation extensively
as a “regulatory checkpoint” in (c...
Methylation of MGMT in GBM
Kaplan-Meier Estimates of Overall Survival in GBM,
According to MGMT Promoter Methylation Statu...
Lab for Bioinformatics and computational genomics

Cancer Stem Cell Theory: the ‘Root’ of Cancer Growth

Tumor
Tumor
Devel...
Lab for Bioinformatics and computational genomics

Gene-specific
Epigenetic
reprogramming
Personalized Medicine
•
•

•

The use of diagnostic tests (aka biomarkers) to identify in advance
which patients are likel...
Biomarker

First used in 1971 … An objective and
« predictive » measure … at the molecular
level … of normal and pathogeni...
Rationale 1:
Why now ? Regulatory path becoming more clear
There is more at stake than
efficient drug
development. FDA
« c...
Why now ?

First and maturing second generation molecular
profiling methodologies allow to stratify clinical
trial partici...
Molecular Profiling

The study of specific patterns (fingerprints) of proteins,
DNA, and/or mRNA and how these patterns co...
Generic Health advice

•Exercise (Hypertrophic Cardiomyopathy)
•Drink your milk (MCM6 Lactose intolarance)
•Eat your green...
Generic Health advice (UNLESS)

•Exercise (Hypertrophic Cardiomyopathy)
•Drink your milk (MCM6 Lactose intolarance)
•Eat y...
Generic Health advice (UNLESS)

•Exercise (Hypertrophic Cardiomyopathy)
•Drink your milk (MCM6 Lactose intolerance)
•Eat y...
Generic Health advice (UNLESS)

•Exercise (Hypertrophic Cardiomyopathy)
•Drink your milk (MCM6 Lactose intolerance)
•Eat y...
Lab for Bioinformatics and computational genomics

Overview
^[now][transl⎮comput]ational[epi]genomic$

•
•
•
•

Who ? Wher...
Genetics
Instrument and Assay providers

G
E
N
E
T
I
C

Whole-genome
sequencing

Enrichment seq
(Exome)

Enrichment
Target...
Lab for Bioinformatics and computational genomics

Overview
^[now][transl⎮comput]ational[epi]genomic$

•
•
•
•

Who ? Wher...
Wobblebase Mission
provide tools to both specialists (researchers,
bioinformaticians, health care providers) and
individua...
PGM: Personal Genomics Manifesto
Everybody who wants to get his genome sequenced has the human right to do so.
No third pa...
Wobblebase Mission
•

change the
diagnostic/healthcare industry
forever by setting a new
standard and empowering the
user
Choosing the Red Pill
The Technical Feasibility Argument
The Quality Argument
The Price Argument
The Logistics around the ...
Notifications
Updates are the single moste
important feature of Wobblebase
#Rs1805007
Bioinformatics
Analysis
pipelines

Social
network
twitter

Wobblebase

Updates
Notifications

eHealth
(fixed
vocabulary)
C...
The Human Microbiome
Christine Rodriguez, Ph.D.
Harvard Outreach 2012

Summer 2012 Workshop in Biology and
Multimedia for ...
Microbes are all over us
There are millions of microbes per
square inch on your body
Thousands of different species on the...
What is the Human Microbiome?
Microbe: tiny living organism, such as bacterium,
fungus, protozoan, or virus
Microbiome: co...
Microbes in the Human Microbiome include species
from each major domain

“Extremophile”
Archaebacteria

Bacteria

Fungi

h...
What features distinguish the
microbial domains?
Bacteria

•Have no nucleus or membrane bound organelles
•Often sphere (co...
Microbes are normally found in and
on the human body
The following sites are “hotspots” for microbial life

Some microbes ...
What’s Happening
in the Nose?
Cilia and mucous
lining trap inhaled
microbes

The nose is a
primary defender
against inhale...
Nose
The interior lining of the nose contains mucous secreting glands. A wide variety of
microbes are normally found there...
Nose
• Aspergillus fungal spores are often
inhaled through the nose. If the immune
system fails to clear these, mold can g...
What’s Happening in
the Oral Cavity?
A wide variety
of microbes
regularly enter
the oral cavity

Brushing and flossing tee...
Oral Cavity
The oral cavity has a wide variety of microbes normally found there. Here’s a few:

Fusobacterium sp.
bacteria...
Oral Cavity
•Prevotella sp. bacteria have natural antibiotic resistance
genes. They can attach to epithelial cells or othe...
What’s Happening
on the Skin?
There are several skin
environments: oily, dry,
moist. Some microbes
prefer one over another...
Skin

• Propionibacterium acnes bacteria colonizes healthy pores, but if pores
become clogged, it grows out of control
• S...
Skin

Trichophyton and Microsporum fungi feast on keratin in the skin
and cause ringworm fungal infections

http://en.wiki...
What’s Happening
in the Gut?
Major barriers for microbes entering the gut:
•low pH
•Saliva and Bile
•Immune system
•Findin...
Gut
Bacteroides thetaiotaomicron
bacteria ferments simple
carbohydrates in the gut,
releasing hydrogen and CO2.
+ carbohyd...
Gut
Ruminococcus sp. bacteria can be found in significantly
high numbers in the gut flora. They break down cellulose
in th...
What’s Happening in the
Urogenital Tract?
Urinary system almost
sterile due to urea and
other chemicals

Introducing a cat...
Urogenital
Lactobacillus
normally maintain
low pH while other
species are kept in
small numbers in
the vagina

Candida alb...
Urogenital
The urinary tract is normally sterile due to urine flushing out the tract.

Urine sample infected with E. coli
...
Interplay Between
Medicine and Microbes

Antibiotics

Chemotherapy drugs

Kills infectious bacteria but also disrupts
natu...
Use of Antimicrobial Products
How many do we really need?

But do we need some
natural exposure to
germs to keep our
norma...
Is My Gut Microbiome the
Same as Yours?
The number and amount
of the many different
microbes can vary greatly
from person ...
Relative amounts of species
Research in the Human Microbiome
Project is starting to identify the relative
amount of each m...
So many new questions to answer
about the Human Microbiome…

How does the gut
flora modify drugs,
and how can we
minimize ...
Lab for Bioinformatics and computational genomics

…$
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2013 10 23_dna_for_dummies_v_presented
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2013 10 23_dna_for_dummies_v_presented
2013 10 23_dna_for_dummies_v_presented
2013 10 23_dna_for_dummies_v_presented
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DNA, an introduction

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  1. 1. Wim Van Criekinge Antwerpen 24 oktober 2013
  2. 2. Lab for Bioinformatics and computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
  3. 3. biobix wvcrieki biobix.be bioinformatics.be 3
  4. 4. EUKARYOTES PROKARYOTES All organisms: 1 or more cells
  5. 5. Lab for Bioinformatics and computational genomics Cell Theory • All organisms are composed of one or more cells. • Cells are the smallest living units of all living organisms. • Cells arise only by division of a previously existing cell.
  6. 6. Each human cell contains 46 chromosomes (except sperm or egg cells)
  7. 7. Lab for Bioinformatics and computational genomics Genetic code DNA
  8. 8. Lab for Bioinformatics and computational genomics
  9. 9. Lab for Bioinformatics and computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body)
  10. 10. Lab for Bioinformatics and computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body) (0.34 × 10-9 m)(6 × 109)(1013) 2.0 × 1013 meters
  11. 11. Lab for Bioinformatics and computational genomics DNA: Structure and Function The human genome comprises the information contained in one set of human chromosomes which themselves contain about 3 billion base pairs (bp) of DNA in 46 chromosomes (22 autosome pairs + 2 sex chromosomes). The total length of DNA present in one adult human is calculated by the multiplication of (length of 1 bp)(number of bp per cell)(number of cells in the body) (0.34 × 10-9 m)(6 × 109)(1013) 2.0 × 1013 meters That is the equivalent of nearly 70 trips from the earth to the sun and back.
  12. 12. Genetic information is stored in the DNA
  13. 13. DNA encodes proteins
  14. 14. “Genes” encode proteins
  15. 15. DNA replication
  16. 16. DNA synthesis and proofreading
  17. 17. Mutations: possible cause of diseases and disfunctionalities
  18. 18. Lab for Bioinformatics and computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
  19. 19. Microbes are all over us There are millions of microbes per square inch on your body Thousands of different species on the skin alone Some thrive on dry patches of the elbow, others thrive in moist environment of armpit It is estimated that there are more microbes in your intestine than there are human cells in your body! http://commons.wikimedia.org/wiki/File:Man_sha dow_-_upper.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  20. 20. Lab for Bioinformatics and computational genomics Defining Epigenetics Genome DNA • Reversible changes in gene expression/function • Without changes in DNA sequence Chromatin Epigenome Gene Expression Phenotype • Can be inherited from precursor cells • Epigenetic information is included in the epigenome • Allows to integrate intrinsic with environmental signals (including diet)
  21. 21. Lab for Bioinformatics and computational genomics Chromatin is a Key Component of Epigenetic Mechanisms
  22. 22. Lab for Bioinformatics and computational genomics Chromatin is a Key Component of Epigenetic Mechanisms Cellular DNA is packaged into a structure called chromatin The unit of chromatin is the nucleosome, a complex of a histone tetramer with approx. 125 bp of DNA wound around it nucleosome histone DNA chromatin • Chromatin organizes genes to be accessible for transcription, replication, and repair
  23. 23. Lab for Bioinformatics and computational genomics Basic Epigenetic Mechanisms: Post Translational Modifications to Histones and Base Changes in DNA • Epigenetic modifications of histones and DNA include: – Histone acetylation and methylation, and DNA methylation Histone Acetylation Ac Histone Methylation Me Me Me DNA Methylation
  24. 24. Lab for Bioinformatics and computational genomics Epigenetic Changes can Alter Chromatin Structure and Regulate Gene Expression TF TF Ac Ac Ac Ac Ac Ac Ac Ac Ac Gene expression • • Gene expression Gene expression (transcription) requires DNA to be physically accessible to transcription factors (TF) Epigenetic changes alter the structure of the chromatin, which determines whether DNA is accessible – Open chromatin allows gene expression – Closed chromatin prevents gene expression
  25. 25. Lab for Bioinformatics and computational genomics
  26. 26. Actionable Epigenome
  27. 27. Lab for Bioinformatics and computational genomics Epigenetics • Epigenetics is essentially the study of how our environment impacts traits acquired within our lifetimes, altering certain gene expressions which may then be passed on to future generations • That is, what we do to our own bodies may affect our children & grandchildren more than we thought. 30
  28. 28. Lab for Bioinformatics and computational genomics Epigenetic (meta)information = stem cells
  29. 29. Lab for Bioinformatics and computational genomics Translational Research towards Personalised Medicine • • DNA diagnostic tests can be used to identify in advance which patients are likely to respond well to a therapy The benefits of this approach are to: – avoid adverse drug reactions – improve efficacy – adjust the dose to suit the patient – differentiate a product in a competitive market – meet future legal or regulatory requirements
  30. 30. Lab for Bioinformatics and computational genomics Historically, Cancer Was Considered to be Driven Mostly by Genetic Changes GENETIC • • • • Example: Replication errors X X Mutations in p53 Activating mutations in RAS Mutations or amplifications of the HER-2 gene Chromosomal translocations in myeloid cells and the generation of the BCR-ABL fusion protein Altered DNA sequence Altered DNA/mRNA/proteins Oncogenesis Tumor
  31. 31. Lab for Bioinformatics and computational genomics Recent Evidence Shows that Epigenetic Changes are Also Important in Causing Cancer GENETIC EPIGENETIC Example: Chromatin modification errors Example: Replication errors X X Altered chromatin structure Altered DNA sequence Altered DNA/mRNA/proteins Oncogenesis Tumor Altered levels of mRNA/proteins
  32. 32. Lab for Bioinformatics and computational genomics Biology uses methylation extensively as a “regulatory checkpoint” in (cancer) development Schuebel et al 2007
  33. 33. Methylation of MGMT in GBM Kaplan-Meier Estimates of Overall Survival in GBM, According to MGMT Promoter Methylation Status Hegi et al. NEJM 2005, 352(10):997-1003 3
  34. 34. Lab for Bioinformatics and computational genomics Cancer Stem Cell Theory: the ‘Root’ of Cancer Growth Tumor Tumor Development and Growth Epigenetically altered, selfrenewing cancer stem cells
  35. 35. Lab for Bioinformatics and computational genomics Gene-specific Epigenetic reprogramming
  36. 36. Personalized Medicine • • • The use of diagnostic tests (aka biomarkers) to identify in advance which patients are likely to respond well to a therapy The benefits of this approach are to – avoid adverse drug reactions – improve efficacy – adjust the dose to suit the patient – differentiate a product in a competitive market – meet future legal or regulatory requirements Potential uses of biomarkers – Risk assessment – Initial/early detection – Prognosis – Prediction/therapy selection – Response assessment – Monitoring for recurrence
  37. 37. Biomarker First used in 1971 … An objective and « predictive » measure … at the molecular level … of normal and pathogenic processes and responses to therapeutic interventions Characteristic that is objectively measured and evaluated as an indicator of normal biologic or pathogenic processes or pharmacologic response to a drug A biomarker is valid if: – It can be measured in a test system with well established performance characteristics – Evidence for its clinical significance has been established
  38. 38. Rationale 1: Why now ? Regulatory path becoming more clear There is more at stake than efficient drug development. FDA « critical path initiative » Pharmacogenomics guideline Biomarkers are the foundation of « evidence based medicine » - who should be treated, how and with what. Without Biomarkers advances in targeted therapy will be limited and treatment remain largely emperical. It is imperative that Biomarker development be accelarated along with therapeutics
  39. 39. Why now ? First and maturing second generation molecular profiling methodologies allow to stratify clinical trial participants to include those most likely to benefit from the drug candidate—and exclude those who likely will not—pharmacogenomicsbased Clinical trials should attain more specific results with smaller numbers of patients. Smaller numbers mean fewer costs (factor 2-10) An additional benefit for trial participants and internal review boards (IRBs) is that stratification, given the correct biomarker, may reduce or eliminate adverse events.
  40. 40. Molecular Profiling The study of specific patterns (fingerprints) of proteins, DNA, and/or mRNA and how these patterns correlate with an individual's physical characteristics or symptoms of disease.
  41. 41. Generic Health advice •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolarance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
  42. 42. Generic Health advice (UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolarance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
  43. 43. Generic Health advice (UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolerance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
  44. 44. Generic Health advice (UNLESS) •Exercise (Hypertrophic Cardiomyopathy) •Drink your milk (MCM6 Lactose intolerance) •Eat your green beans (glucose-6-phosphate dehydrogenase Deficiency) •& your grains (HLA-DQ2 – Celiac disease) •& your iron (HFE - Hemochromatosis) •Get more rest (HLA-DR2 - Narcolepsy)
  45. 45. Lab for Bioinformatics and computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
  46. 46. Genetics Instrument and Assay providers G E N E T I C Whole-genome sequencing Enrichment seq (Exome) Enrichment Targeted Panels PCR bp Full genome 109 108 107 106 105 104 103 CLIA Lab service providers Confidential Information | ©2013 MDxHealth Inc. All rights reserved. 102 101 1
  47. 47. Lab for Bioinformatics and computational genomics Overview ^[now][transl⎮comput]ational[epi]genomic$ • • • • Who ? Where ? Bioinformatics (Epi)genetics Technology: Next Gen Sequencing • Personal Genomics
  48. 48. Wobblebase Mission provide tools to both specialists (researchers, bioinformaticians, health care providers) and individual consumers that unlock the power of genomic data to the USER enable personalized genomics today by simplifying the way we organize, visualize and manage genomic data.
  49. 49. PGM: Personal Genomics Manifesto Everybody who wants to get his genome sequenced has the human right to do so. No third party can own your genetic data, your genetic data is exclusively yours. Nobody can be forced to get his genome analyzed or to reveal his genome to a third party. Your genome should allways be treated as confidential, private information. People should be advised not to share their identity AND their entire genome on a public forum. People should be advised to use secure technologies that allow to maximally protect phenotypic and/or genotype data. People should be able to actively explore, manage and get updated interpretation on their genomic data.
  50. 50. Wobblebase Mission • change the diagnostic/healthcare industry forever by setting a new standard and empowering the user
  51. 51. Choosing the Red Pill The Technical Feasibility Argument The Quality Argument The Price Argument The Logistics around the sample on howto manage the data Argument The Ethical debate The Privacy/Security concern
  52. 52. Notifications Updates are the single moste important feature of Wobblebase
  53. 53. #Rs1805007
  54. 54. Bioinformatics Analysis pipelines Social network twitter Wobblebase Updates Notifications eHealth (fixed vocabulary) Comparison
  55. 55. The Human Microbiome Christine Rodriguez, Ph.D. Harvard Outreach 2012 Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  56. 56. Microbes are all over us There are millions of microbes per square inch on your body Thousands of different species on the skin alone Some thrive on dry patches of the elbow, others thrive in moist environment of armpit It is estimated that there are more microbes in your intestine than there are human cells in your body! http://commons.wikimedia.org/wiki/File:Man_sha dow_-_upper.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  57. 57. What is the Human Microbiome? Microbe: tiny living organism, such as bacterium, fungus, protozoan, or virus Microbiome: collectively all the microbes in the human body; a community of microbes Biofilm: a community of microbes that live together on a surface Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  58. 58. Microbes in the Human Microbiome include species from each major domain “Extremophile” Archaebacteria Bacteria Fungi http://en.wikipedia.org/wiki/File:Aspergillus_niger_01.jpg http://en.wikipedia.org/wiki/File:SalmonellaNIAID.jpg http://en.wikipedia.org/wiki/File:Grand_prismatic_spring.jpg http://commons.wikimedia.org/wiki/File:Tree_of_life.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  59. 59. What features distinguish the microbial domains? Bacteria •Have no nucleus or membrane bound organelles •Often sphere (cocci) or rod (bacillus) shape, but others as well Generalized bacteria and archaebacteria cell Archeabacteria •Have no nucleus or membrane bound organelles •Can look similar to bacteria or drastically different shapes, such as flat and square •Have some metabolic similarities to eukaryotes Eukaryotes •Have a true nucleus and membrane bound organelles •Wide variety of shapes. For this presentation, we will focus on fungi •Fungi are unique since they have a cell wall and form spores during reproduction eneralized eukaryotic cell http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=CELL006B&File_type=GIF http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=BACT003B&File_type=GIF Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  60. 60. Microbes are normally found in and on the human body The following sites are “hotspots” for microbial life Some microbes are native, normally found in the body Let’s explore these five regions Some microbes are introduced, suddenly arriving at a new residence in the body http://nihroadmap.nih.gov/hmp/ Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  61. 61. What’s Happening in the Nose? Cilia and mucous lining trap inhaled microbes The nose is a primary defender against inhaled pathogens Inflammation from viral infection and allergic reactions Inhaled medicines and oral antibiotics There is a delicate balance of microbes that are maintained to keep that environment healthy. Weakened immune systems can throw off that balance and allow the wrong microbes to grow out of control. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg
  62. 62. Nose The interior lining of the nose contains mucous secreting glands. A wide variety of microbes are normally found there. Here’s a few: • Staphylococcus epidermidis bacteria forms a biofilm that coats the mucosal lining • Staphylococcus aureus bacteria is fine when kept under control by a protease found in S. epidermidis, but if left to grow out of control, S. aureus can become pathogenic and cause infection Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg http://en.wikipedia.org/wiki/File:MRSA7820.jpg http://en.wikipedia.org/wiki/File:Staphylococcus_epidermidis_01.png
  63. 63. Nose • Aspergillus fungal spores are often inhaled through the nose. If the immune system fails to clear these, mold can grow in the lungs •Corneybacterium accolens bacteria is rarely a pathogen, but if it enters the bloodstream due to a torn blood vessel, it can cause serious infections Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Human-nose.jpg http://en.wikipedia.org/wiki/File:Corynebacterium_ulcerans_01.jpg http://en.wikipedia.org/wiki/File:Aspergillus.jpg http://en.wikipedia.org/wiki/File:Aspergillus_fumigatus_Invasive_Disease_Mechanism_Diagram.jpg
  64. 64. What’s Happening in the Oral Cavity? A wide variety of microbes regularly enter the oral cavity Brushing and flossing teeth clears some built up biofilm saliva, pH, temperature, immune system prevent many species from surviving Oral antibiotics inhibit growth Symbiosis of the oral microbes that are able to survive these conditions form an elaborate scaffold that lives on the tooth enamel and at the interface with the gums. It forms a barrier for incoming bacteria. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg
  65. 65. Oral Cavity The oral cavity has a wide variety of microbes normally found there. Here’s a few: Fusobacterium sp. bacteria is a larger bacteria that helps form a scaffold for many other bacteria in the oral biofilm http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers Streptococcus mitis bacteria typically forms a biofilm on the hard enamel surfaces of the teeth. If gums get inflamed, it can enter the bloodstream and cause infection
  66. 66. Oral Cavity •Prevotella sp. bacteria have natural antibiotic resistance genes. They can attach to epithelial cells or other bacteria and cause larger infections in inflamed areas. • Candida albicans fungus can cause oral infection known as thrush http://microbewiki.kenyon.edu/index.php/File:P_ruminicola.jpg http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Thrush.JPG http://en.wikipedia.org/wiki/File:Candida_albicans_2.jpg
  67. 67. What’s Happening on the Skin? There are several skin environments: oily, dry, moist. Some microbes prefer one over another. The skin has natural defenses including slightly acidic sweat and antimicrobial peptides. Microbes hide in crevices to recolonize skin after washing with soap Antibiotic washes and oral antibiotics disturb normal balance of microbes on the skin There is a normal balance of microbes on the skin that protect introduced microbes from harming us. Damaged skin gives opportunities for microbes to invade the bloodstream and cause serious illness. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg
  68. 68. Skin • Propionibacterium acnes bacteria colonizes healthy pores, but if pores become clogged, it grows out of control • Staphylococcus epidermidis bacteria normally colonizes on the skin. But when P. acnes clogs pores, S. epidermidis also grows out of control in the infected pores • Staphylococcus aureus bacteria can also infect clogged pores like Staph epidermidis. Even worse, many antibiotic resistant strains of Staph aureus make it difficult to treat the infection. http://microbewiki.kenyon.edu/index.php/File:Lesionsmicro.jpg http://microbewiki.kenyon.edu/index.php/File:Lesionsclosed.jpg http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  69. 69. Skin Trichophyton and Microsporum fungi feast on keratin in the skin and cause ringworm fungal infections http://en.wikipedia.org/wiki/File:Yeartinfection.JPG http://commons.wikimedia.org/wiki/File:Anterior_view_of_male_upper_body,_retouched.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  70. 70. What’s Happening in the Gut? Major barriers for microbes entering the gut: •low pH •Saliva and Bile •Immune system •Finding a place to attach to intestinal wall •Surviving a widely varied diet For those microbes that manage to colonize the gut: •gut flora perform regular tasks of digestion, vitamin production, many others • Gene transfer between the myriad of species in the gut can generate new combinations of drug resistant “superbugs” http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  71. 71. Gut Bacteroides thetaiotaomicron bacteria ferments simple carbohydrates in the gut, releasing hydrogen and CO2. + carbohydrates CO2 and H2 Methanobrevibacter smithii archeabacteria consumes hydrogen gas from Bacteroides and produces methane, which is lost from gut as “gas” http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers CH4 Methane Gas
  72. 72. Gut Ruminococcus sp. bacteria can be found in significantly high numbers in the gut flora. They break down cellulose in the gut, helping with digestion. Helicobacter pylori bacteria has a helical shape and colonizes the stomach and upper G.I. tract. It is known to be a major cause of stomach ulcers, although many with H. pylori do not get ulcers. http://microbewiki.kenyon.edu/index.php/File:G_reaction1.jpg http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Helicobacter_pylori_diagram.png
  73. 73. What’s Happening in the Urogenital Tract? Urinary system almost sterile due to urea and other chemicals Introducing a catheter into the urethra can introduce microbes directly into the bladder, where a biofilm can grow and cause bladder infection Urine often flushes out microbes that find their way in The vagina has a low pH due to Lactobacillus secreting lactic acid and hydrogen peroxide. Let’s explore the microbiome of this region further. Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg
  74. 74. Urogenital Lactobacillus normally maintain low pH while other species are kept in small numbers in the vagina Candida albicans can take over and cause a yeast infection If Lactobacillus decreases from antibiotics… Lactobacillus and vaginal epithelial cell G. vaginalis and vaginal epithelial cell Gardnerella vaginalis can grow too much and cause bacterial vaginosis. http://commons.wikimedia.org/wiki/File:Lactobacillus_sp_01.png http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Candida_albicans_2.jpg
  75. 75. Urogenital The urinary tract is normally sterile due to urine flushing out the tract. Urine sample infected with E. coli Urine sample infected with E. coli But, Escherichia coli from GI tract can infect urinary tract due to poor hygiene and contamination from nearby GI tract opening. http://commons.wikimedia.org/wiki/File:Female_Genital_Organs.svg Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://commons.wikimedia.org/wiki/File:E_choli_Gram.JPG http://commons.wikimedia.org/wiki/File:Pyuria2011.JPG
  76. 76. Interplay Between Medicine and Microbes Antibiotics Chemotherapy drugs Kills infectious bacteria but also disrupts natural flora. Can result in yeast infections, digestive problems, etc. http://commons.wikimedia.org/wiki/File:Chemotherapy_bottles_NCI.jpg http://commons.wikimedia.org/wiki/File:NOVAMOXIN_antibiotic.jpg Gut flora has been shown to modify some drugs during metabolism. This causes many side effects, including upset stomach. Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  77. 77. Use of Antimicrobial Products How many do we really need? But do we need some natural exposure to germs to keep our normal flora around? Products kill germs to reduce infection http://commons.wikimedia.org/wiki/File:Afwasmiddel.jpg http://commons.wikimedia.org/wiki/File:Tissue.jpg http://commons.wikimedia.org/wiki/File:Refill_soap.jpg http://commons.wikimedia.org/wiki/File:Toothpaste.jpg http://commons.wikimedia.org/wiki/File:Hands-Clapping.jpg Summer 2012 Workshop in Biology and Multimedia for High School Teachers Will this allow “superbugs” that can barely survive these treatments to grow and become more prevalent…causing problems for the future?
  78. 78. Is My Gut Microbiome the Same as Yours? The number and amount of the many different microbes can vary greatly from person to person. Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  79. 79. Relative amounts of species Research in the Human Microbiome Project is starting to identify the relative amount of each microbe present at different locations in the body. The Microbiome of one person can be different than others in species and relative amounts Summer 2012 Workshop in Biology and Multimedia for High School Teachers http://en.wikipedia.org/wiki/File:Skin_Microbiome20169-300.jpg
  80. 80. So many new questions to answer about the Human Microbiome… How does the gut flora modify drugs, and how can we minimize side effects? Are we making germs more resistant to anitmicrobials? What happens when the germs are resistant to all of the drugs in our arsenal? Why does my gut flora look different than yours? How does that affect obesity, food allergies, and ability to fight disease? What do you want to know? http://commons.wikimedia.org/wiki/File:Hands-Clapping.jpg http://commons.wikimedia.org/wiki/File:Chemotherapy_bottles_NCI.jpg http://commons.wikimedia.org/wiki/File:Intestine_and_stomach_-_transparent_-_cut.png Summer 2012 Workshop in Biology and Multimedia for High School Teachers
  81. 81. Lab for Bioinformatics and computational genomics …$

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