Lets start by Refreshing Memories In reminiscence of a time, when - - PowerPoint PPT Presentation

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Lets start by Refreshing Memories In reminiscence of a time, when - - PowerPoint PPT Presentation

Lets start by Refreshing Memories In reminiscence of a time, when we were striving to built computation devices from technical modules with defined functions to perform complex operations In reminiscence of a time after that, when we


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SLIDE 1

Let’s start by Refreshing Memories… In reminiscence of a time, when we were striving to built computation devices from technical modules with defined functions to perform complex operations… In reminiscence of a time after that, when we were seeking to create self-replicating, sustainable systems from biological bricks to understand life… In reminiscence of a time after that, when we were aiming at the

  • ptimization of our own life based on trillions of foreign cells,

bacteria, inside us… That time is now…

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SLIDE 2

Hacking the Human Microbiome

  • Dr. Lorenz K. Adlung

@lorenzadlung 29/12/2018 Leipzig, Germany

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29/12/2018 | Slide 3

  • Dr. Lorenz K. Adlung

@lorenzadlung

  • 1. What is the Human Microbiome?
  • 2. How can we study the Human Microbiome?
  • 3. Is there a reasonable hype about the subject?
  • 4. Where are the most demanding challenges?

General questions to lay the foundation for future perspectives

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29/12/2018 | Slide 4

  • Dr. Lorenz K. Adlung

@lorenzadlung

  • 1. What is the Human Microbiome?
  • 2. How can we study the Human Microbiome?
  • 3. Is there a reasonable hype about the subject?
  • 4. Where are the most demanding challenges?

General questions to lay the foundation for future perspectives

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29/12/2018 | Slide 5

  • Dr. Lorenz K. Adlung

@lorenzadlung

3,000,000,000

  • 1

5,000,000

  • 1,000

ATGGGACCTCTCCACCAGTTTCTCC TGCTGCTGATCACAGCCCTGTCCCA AGCCCTCAACACCACGGTGCTGCA GGGCATGGCCGGCCAGTCCTTGAG GGTGTCATGTACTTATGACGCCTTG AAGCACTGGGGGAGACGCAAGGCC TGGTGTCGGCAGCTGGGTGAGGAG GGCCCATGCCAGCGTGTGGTGAGC ACACACGGTGTGTGGCTGCTGGCC TTCCTGAAGAAGCG…

A simple computation underlines the complexity of the microbiome

∑ ∑

ATGAGCAAAATCAGGG TGTTATCTGTCGATGATT CGGCACTGATGCGCCAG ATCATGACAGAAATCATCAACAGCCATAGC GACATGGAAATGGTGGCGACCGCGC…

40,000,000,000,000 40,000,000,000,000 5,000,000,000,000

doi.org/10.1371/ journal.pbio.1002533

WHAT?

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29/12/2018 | Slide 6

  • Dr. Lorenz K. Adlung

@lorenzadlung

  • Human Microbiome = All bacteria that live inside us.

Sites of human microbiome:

  • Skin
  • Mouth
  • Airways
  • Spinal cord (?)
  • Gastrointestinal tract

The Human Microbiome is a complex community, diverse and highly adapted. The definition of the Human Microbiome implies subsets of microbes

!

WHAT?

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29/12/2018 | Slide 7

  • Dr. Lorenz K. Adlung

@lorenzadlung

Bacteria with common origin and size but specific niche adaptations

  • xygen

sugar fat ✅

!

~10-6m = 1µm WHAT?

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29/12/2018 | Slide 8

  • Dr. Lorenz K. Adlung

@lorenzadlung

!

Complex interactions within diverse bacterial communities inside us

WHAT? ? ? ? ?

! ! !

⚙ ⚙ ⚙ ⚙

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  • Dr. Lorenz K. Adlung

@lorenzadlung

!

Molecular signalling and response mechanisms in bacteria

WHAT?

⚙⚙ ⚙ ⚙ ⚙ ⚙

! ! ! !

! "

Refreshing Memories Adaptation

http://junq.info/?p=1079

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  • Dr. Lorenz K. Adlung

@lorenzadlung

relative amount

Dynamic behaviour of bacterial growth and depletion characteristics

WHAT?

time amount stability resilience

  • utgrowth

extinction

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29/12/2018 | Slide 11

  • Dr. Lorenz K. Adlung

@lorenzadlung

  • 1. What is the Human Microbiome?
  • 2. How can we study the Human Microbiome?
  • 3. Is there a reasonable hype about the subject?
  • 4. Where are the most demanding challenges?

General questions to lay the foundation for future perspectives

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29/12/2018 | Slide 12

  • Dr. Lorenz K. Adlung

@lorenzadlung

  • extraction and analysis outside of the living animal

Detection of the Human Microbiome through cultivation

HOW?

  • xygen

sugar 1 1

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29/12/2018 | Slide 13

  • Dr. Lorenz K. Adlung

@lorenzadlung

Measurement of the Human Microbiome by shotgun sequencing

HOW?

ATGAGCAAAATCAGGGTGTTATCTGTCGATGATTCGGCACTGATG CGCCAGATCATGACAGAAATCATCAACAGCCATAGCGACATGGA AATGGTGGCGACCGCGCCTGATCCGCTGGTCGCGCGTGACTTG ATTAAGAAATTCAATCCCGATGTGCTGACGCTGGATGTTGAAATG CCGCGGATGGACGGACTGGATTTCCTCGAAAAATTAATGCG…

fragmentation reading alignment reference matching inference

!

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  • Dr. Lorenz K. Adlung

@lorenzadlung

Uncertainties are propagated in every step of the analysis

HOW?

1 2 3 … n

!1 NA NA NA 1 NA !2 NA 1 NA NA NA !… NA NA 1 NA NA !m 1 NA NA NA 1

"

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  • Dr. Lorenz K. Adlung

@lorenzadlung

Characterization of the Human Microbiome in health/disease contexts

! !

" #

HOW?

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  • Dr. Lorenz K. Adlung

@lorenzadlung

  • n-dimensional feature space
  • rational interventions

Link between bacteria and body weight: From correlation to cause?

HOW?

amount bacterium body weight

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29/12/2018 | Slide 17

  • Dr. Lorenz K. Adlung

@lorenzadlung

  • 1. What is the Human Microbiome?
  • 2. How can we study the Human Microbiome?
  • 3. Is there a reasonable hype about the subject?
  • 4. Where are the most demanding challenges?

General questions to lay the foundation for future perspectives

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29/12/2018 | Slide 18

  • Dr. Lorenz K. Adlung

@lorenzadlung

Y

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  • Dr. Lorenz K. Adlung

@lorenzadlung

Contribution to:

  • Eating habits
  • Fitness state
  • Susceptibility for infections
  • Aging
  • Cancer

The Human Microbiome and its therapeutic potential hyped in the media

HYPE?

"Yesterday I interviewed a respected scientist of the comp- bio field who told me that the best diet for obese people is eating poop of lean people and let their gut microbiome work” Dror Feuer @drorfo Twitter, 28/12/2017

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  • Dr. Lorenz K. Adlung

@lorenzadlung

Subtraction of bacteria: Antibiotics and phage therapy

HYPE? ! " " " # "

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29/12/2018 | Slide 21

  • Dr. Lorenz K. Adlung

@lorenzadlung

Multiplication of bacteria through growth stimulation: Prebiotics

HYPE? !

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  • Dr. Lorenz K. Adlung

@lorenzadlung

Addition of bacteria: Faecal transplantations, probiotics, vaccinations

HYPE? ! " # ! $ % & & &

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  • Dr. Lorenz K. Adlung

@lorenzadlung

Division of bacteria through dilution of resources: Fasting

HYPE? !

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29/12/2018 | Slide 24

  • Dr. Lorenz K. Adlung

@lorenzadlung

  • 1. What is the Human Microbiome?
  • 2. How can we study the Human Microbiome?
  • 3. Is there a reasonable hype about the subject?
  • 4. Where are the most demanding challenges?

General questions to lay the foundation for future perspectives

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29/12/2018 | Slide 25

  • Dr. Lorenz K. Adlung

@lorenzadlung

  • despite available tools: Biosafety first !"#$%
  • ethical standards for handling metagenome code &'
  • patenting of genetic sequences from the Human Microbiome? ()
  • sharing of sequenced diversity *+

The Human Microbiome harbours a huge therapeutic potential that can only be harnessed if we share information faithfully. Do-it-yourself engineering of the Human Microbiome in its infancy CHALLENGES? #scicomm

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29/12/2018 | Slide 26

  • Dr. Lorenz K. Adlung

@lorenzadlung

Acknowledgement of an interdisciplinary, social, scientific environment

All medically-relevant pictures from https://smart.servier.com/ under Creative Commons Attribution 3.0 Unported License

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SLIDE 27

Let’s end by Refreshing Memories… The Human Microbiome is a complex ensemble of bacteria with non-intuitive interactions and inter-dependencies… We are exploring mechanisms of regulation through Hacking by rational interference under controlled conditions… Individuals try to monopolize technology, knowledge and data, constraining free and open research, rendering the potential of Hacking the Human Microbiome a threat through uneducated trials… That time is over… @lorenzadlung