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

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 optimization of our own life based on trillions of foreign cells, bacteria, inside us… That time is now…

29/12/2018 Hacking the Human Microbiome Dr. Lorenz K. Adlung @lorenzadlung Leipzig, Germany

General questions to lay the foundation for future perspectives Author Division Page3 12/29/18 | 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? 29/12/2018 | Slide 3 Dr. Lorenz K. Adlung @lorenzadlung

General questions to lay the foundation for future perspectives Author Division Page4 12/29/18 | 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? 29/12/2018 | Slide 4 Dr. Lorenz K. Adlung @lorenzadlung

WHAT? A simple computation underlines the complexity of the microbiome Author Division 3,000,000,000 ATGGGACCTCTCCACCAGTTTCTCC Page5 12/29/18 | TGCTGCTGATCACAGCCCTGTCCCA AGCCCTCAACACCACGGTGCTGCA � GGGCATGGCCGGCCAGTCCTTGAG GGTGTCATGTACTTATGACGCCTTG 5,000,000,000,000 1 40,000,000,000,000 AAGCACTGGGGGAGACGCAAGGCC ∑ ∑ TGGTGTCGGCAGCTGGGTGAGGAG GGCCCATGCCAGCGTGTGGTGAGC ACACACGGTGTGTGGCTGCTGGCC TTCCTGAAGAAGCG… 5,000,000 � ATGAGCAAAATCAGGG doi.org/10.1371/ 40,000,000,000,000 1,000 TGTTATCTGTCGATGATT journal.pbio.1002533 CGGCACTGATGCGCCAG ATCATGACAGAAATCATCAACAGCCATAGC GACATGGAAATGGTGGCGACCGCGC… 29/12/2018 | Slide 5 Dr. Lorenz K. Adlung @lorenzadlung

WHAT? The definition of the Human Microbiome implies subsets of microbes Author Division • Human Microbiome = All bacteria that live in side us. Page6 12/29/18 | Sites of human microbiome: ! • Skin • Mouth • Airways • Spinal cord (?) • Gastrointestinal tract The Human Microbiome is a complex community, diverse and highly adapted. 29/12/2018 | Slide 6 Dr. Lorenz K. Adlung @lorenzadlung

WHAT? Bacteria with common origin and size but specific niche adaptations Author Division Page7 12/29/18 | ~10 -6 m ! = 1µm oxygen ✅ sugar fat 29/12/2018 | Slide 7 Dr. Lorenz K. Adlung @lorenzadlung

WHAT? Complex interactions within diverse bacterial communities inside us Author Division ! Page8 12/29/18 | ⚙ ⚙ ? ? ! ! ⚙ ⚙ ? ? ! 29/12/2018 | Slide 8 Dr. Lorenz K. Adlung @lorenzadlung

WHAT? Molecular signalling and response mechanisms in bacteria Author Division Page9 12/29/18 | ! ⚙ Refreshing ! Memories ⚙ ! ⚙ " Adaptation ! ⚙ ! ⚙ ⚙ http://junq.info/?p=1079 ! 29/12/2018 | Slide 9 Dr. Lorenz K. Adlung @lorenzadlung

WHAT? Dynamic behaviour of bacterial growth and depletion characteristics Author Division Page10 12/29/18 | relative amount amount outgrowth resilience stability extinction time 29/12/2018 | Slide 10 Dr. Lorenz K. Adlung @lorenzadlung

General questions to lay the foundation for future perspectives Author Division Page11 12/29/18 | 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? 29/12/2018 | Slide 11 Dr. Lorenz K. Adlung @lorenzadlung

HOW? Detection of the Human Microbiome through cultivation Author Division • extraction and analysis outside of the living animal Page12 12/29/18 | oxygen 0 1 0 sugar 1 29/12/2018 | Slide 12 Dr. Lorenz K. Adlung @lorenzadlung

HOW? Measurement of the Human Microbiome by shotgun sequencing Author Division ATGAGCAAAATCAGGGTGTTATCTGTCGATGATTCGGCACTGATG Page13 12/29/18 | CGCCAGATCATGACAGAAATCATCAACAGCCATAGCGACATGGA AATGGTGGCGACCGCGCCTGATCCGCTGGTCGCGCGTGACTTG ATTAAGAAATTCAATCCCGATGTGCTGACGCTGGATGTTGAAATG CCGCGGATGGACGGACTGGATTTCCTCGAAAAATTAATGCG… fragmentation reading alignment ! ⚙ matching inference reference 29/12/2018 | Slide 13 Dr. Lorenz K. Adlung @lorenzadlung

HOW? Uncertainties are propagated in every step of the analysis Author Division Page14 12/29/18 | 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 29/12/2018 | Slide 14 Dr. Lorenz K. Adlung @lorenzadlung

HOW? Characterization of the Human Microbiome in health/disease contexts Author Division Page15 12/29/18 | " # ! ! 29/12/2018 | Slide 15 Dr. Lorenz K. Adlung @lorenzadlung

HOW? Link between bacteria and body weight: From correlation to cause? Author Division • n-dimensional feature space Page16 12/29/18 | body weight amount bacterium • rational interventions 29/12/2018 | Slide 16 Dr. Lorenz K. Adlung @lorenzadlung

General questions to lay the foundation for future perspectives Author Division Page17 12/29/18 | 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? 29/12/2018 | Slide 17 Dr. Lorenz K. Adlung @lorenzadlung

Y Author Division Page18 12/29/18 | 29/12/2018 | Slide 18 Dr. Lorenz K. Adlung @lorenzadlung

HYPE? The Human Microbiome and its therapeutic potential hyped in the media Author Division Contribution to: Page19 12/29/18 | "Yesterday I interviewed a • Eating habits respected scientist of the comp- • Fitness state bio field who told me that the best diet for obese people is eating • Susceptibility for infections poop of lean people and let their • Aging gut microbiome work” • Cancer Dror Feuer @drorfo Twitter, 28/12/2017 29/12/2018 | Slide 19 Dr. Lorenz K. Adlung @lorenzadlung

HYPE? Subtraction of bacteria: Antibiotics and phage therapy Author Division Page20 12/29/18 | " " ! # " " 29/12/2018 | Slide 20 Dr. Lorenz K. Adlung @lorenzadlung

HYPE? Multiplication of bacteria through growth stimulation: Prebiotics Author Division Page21 12/29/18 | ! 29/12/2018 | Slide 21 Dr. Lorenz K. Adlung @lorenzadlung

HYPE? Addition of bacteria: Faecal transplantations, probiotics, vaccinations Author Division Page22 12/29/18 | ! & $ ! # % " & & 29/12/2018 | Slide 22 Dr. Lorenz K. Adlung @lorenzadlung

HYPE? Division of bacteria through dilution of resources: Fasting Author Division Page23 12/29/18 | ! 29/12/2018 | Slide 23 Dr. Lorenz K. Adlung @lorenzadlung

General questions to lay the foundation for future perspectives Author Division Page24 12/29/18 | 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? 29/12/2018 | Slide 24 Dr. Lorenz K. Adlung @lorenzadlung

Do-it-yourself engineering of the Human Microbiome in its infancy CHALLENGES? Author Division • despite available tools: Biosafety first !"#$% Page25 12/29/18 | • ethical standards for handling metagenome code &' • patenting of genetic sequences from the Human Microbiome? () • sharing of sequenced diversity *+ #scicomm The Human Microbiome harbours a huge therapeutic potential that can only be harnessed if we share information faithfully. 29/12/2018 | Slide 25 Dr. Lorenz K. Adlung @lorenzadlung

Acknowledgement of an interdisciplinary, social, scientific environment Author Division Page26 12/29/18 | All medically-relevant pictures from https://smart.servier.com/ under Creative Commons Attribution 3.0 Unported License 29/12/2018 | Slide 26 Dr. Lorenz K. Adlung @lorenzadlung

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