Setting the path for world wide Life Sciences Research

Transcription

1 Setting the path for world wide Life Sciences Research

2 OPPORTUNITY Arguments Goals Means

3 Arguments Unmet needs Dairy Enterprise Leveraged Resources

4 The Reality of 2012 We should be enjoying the greatest health in history and some are,..but most are not Jaring Timmerman Roger Gentilhomme

5 Global Agricultural Enterprise The big challenge: Agriculture 2.0 Health, Safety & Sustainability The goal: Integrating biological systems to enhance value, diversity, health, safety, delight and sustainability throughout the food supply. Agribusiness Farmers Food Industry Consumers

6 Quantity Agriculture is Unsustainable What more do you need to say? Food for SUV s!!!!

7 Value of Milk What is the price of milk as a beverage today in California Sacramento airport: Water $2.49 Milk $2.25

8 Value of Milk? According to price, California farmers lower the value of water by passing it through their cows!

9 Production 600 million tons!

10 ASSETS Scientific and Biological Resources

11 The 21st Century Biology - Evolution Integrative Industrialization of Organisms and Systems for Individuals

12 21 st Century Chemistry Comprehensive Entire classes of molecules Sensitive Parts per trillion Accurate Detailed complex structures

13 21 st Century Mathematics Computational methods Massive Databases Annotating Genomes to Neighborhood Maps Global networks Economies to Ecosystems Industrialization of Research Egalitarianism of Knowledge Courtesy Matthias Friedrich

14 -AND- 21 st Century Engineering Complex Systems measure adjust measure - adjust Devices Fast, furious, cheap Smart Processing Networked, controlled

15 Genomics: the Footsteps of Evolution Humans: Plants: Animals Microorganisms: What can they tell us about Diet and Health?

16 Evolutionary Nutrition What evolved under the Darwinian Pressure to be Nourishing?

17 Lactation The Darwinian Engine of Nutrition Maternal Optima Benefits B<C Costs Time Infant Optima B<(r)C Evolving a cost benefit solution for Katie Hinde UCLA Health

18 Milk Genomics Consortium Coordinating world wide resources to assemble, annotate and validate the subset of mammalian genomes responsible for milk: The Milk Genome Proteomics Glycomics Lipidomics Health Expression analysis

19 Origins of Milk Evolutionary Relationship of Mammary Development and Reproductive Strategy Mammals Egg Laying Live Birth No Placenta Full Placenta Reproductive Status Egg Laying Live Birth Placenta Mammary Anatomy Anatomy Nipple Complete Relative Mammary Development None Preavian Monotremes Marsupials Advanced Mammals Complete None or Rudimentary None None Complex: Ductular/ Alveolar Tree Organized Pad/Gland Diffuse Pad None + + Hair or Groove None Evolutionary Time F. Schanbacher - 9/95

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21 2004 Napa IMGC Symposia 2005 Napa 2006 Brussels 2007 Napa 2008 Sydney 2009 Paris 9 years of International meetings consortia and collaborative research programs 2010 UC Davis 2011 Sydney 2012 Wageningen

22 a Team Approach Adrian Molenaar Angie Hinrichs Bill Martin Bruce German Danielle Lemay David Lynn Evgenia Kriventseva Evgeny Zdobnov Gonzalo Rincon Juan Medrano Katie Pollard Monique Rijnkels Nauman Maqbool Peggy Neville Ross Tellam Theresa Casey Wes Barris

23 The Thematic principle Concept: Evolutionary Nutrition Example: milk, the Rosetta stone of nourishment Mechanistic targets for. health and prevention

24 GOALS Global Aspirational BIG

25 GOALS Global Aspirational BIG

26 Allergy/Atopy The world is suffering through increasing incidence and severity of autoimmunity

27 Allergy/Atopy Atopic disease is inexplicably getting more frequent and severe Raw milk is tantalizingly protective

28 Return on Investment Value of Milk? Today: American Academy of Pediatrics recommends NO Cow s milk until the first birthday due to concerns about allergy!

29 Inflammation Inflammation drives all noncommunicable degenerative diseases

30 Activation of TLRs & NLRs The toll like receptors & NOD like receptors evolved as innate sentinels to microbial signals. Chemicals and specific nutrients in foods act as agonists and antagonists to these receptors and their downstream signaling pathways. Saturated fatty acids are TLR4 agonists Omega-3 fatty acids are TLR4 antagonists

31 Intestinal Microbiota Pathogenic bacteria make up a finite proportion of the intestinal microbiota. Their activation and proliferation promotes inflammatory activation of intestinal cells Commensal bacteria displace pathogens, secrete antimicrobial agents, and guide immune and epithelial function and development in the host

32 Barrier Integrity The integrity of cell junctions in the gut is critical to maintaining a barrier to the translocation of biomolecules into circulation Migration of bacterial products through the epithelial barrier promotes inflammatory activation of circulating cells Commensal bacteria and ingested beneficial bacteria restore barrier integrity

33 Adipose Dysfunction Excess adipose stimulates resident macrophages that recruit a net inflammatory distribution of immune cells into the tissue.

34 Growth on milk oligosaccharides helps some bifidobacteria bind intestinal cells Caco-2 HT-29 Chichlowski et al JPGN 2012

35 Growth on milk oligosaccharides modulates tight junction protein expression Caco-2 Chichlowski et al JPGN 2012

36 HMO-grown Bifidobacteria induce antiinflammatory cytokines Caco-2 Chichlowski et al JPGN 2012

37 Bifidobacteria grown on HMO impact the Gut Brain Axis Vagal afferent neurons transmission to CNS Parasympathetic efferent outflow - gastric function - pancreatic function - hepatic glucose utilization Higher brain function change in behavior Enteroendocrine cells luminal chemosensors R21 Helen Raybould UCD Vet School

38 Return on Investment Value of Milk? Today: Cardiologists recommend avoiding all dairy products!

39 The Rumen The annual release of methane is approximately 80 million metric tons 50% of saturated fat and 100% of trans is due to rumen

40 The Rumen Bacterial Community Bryan A. White University of Illinois at Urbana-Champaign

41 The Rumen Metabolism Cellulosic feeds Rumen Bacteria (10 10 ml -1 ) Volatile fatty acids (serve as a source of energy for host)

42 Return on Investment Value of Milk? Tomorrow: Methane captured, Energy gained, Rumen is a bioreactor for bioactives.

43 Agenda 1 Recruit ideas 2 Establish consensus 3 Recruit teams 4 Drive Grants 5 Coordinate Program 6 Strategy for Translation

44 Means 1. Lactation inspired Integrative Research 2. Translation to Practice 3. Education

45 Translation Milk allows us a different model: Parallel R&D

46 Parallel Model of Research Ingredient & Product Optimization Molecular Characterization of Milk (Composition/Structure/Abundance) Identify Function Mechanism of Action Demonstrate Benefit BRING TO PRACTICE Health Assessment/Diagnostics

47 Our Strategic Model Translational Science Translating from bench to products Translating from health needs to bench

48 Reverse Translation Convergent Deduction Bench Science Translating from unpredicted human outcomes to scientific discovery of causal mechanism

49 Key to Success Bench Science Reverse Translation Everyone must: Understand the problem i.e. what don t we know

50 Statistical Design Reverse Translation Bench Science One large coordinated Project Tolerate type 1 errors (false positive) = low α Avoid type 2 errors (false negative) = high β

51 Divergent Innovation Forward Translation Bench Discovery Consumer Products Consumer Products Consumer Products Services Services Services Translating from a single breakthrough in understanding to multiple products and services

52 Key to Success Forward Translation Bench Discovery Services Services Services Consumer Products Consumer Products Consumer Products Everyone must: Understand the breakthrough i.e. what do we, only now, know

53 Statistical Design Forward Translation Bench Discovery Services Services Services Consumer Products Consumer Products Consumer Products High N Many Small Independent Projects Tolerate type 2 errors = low β Avoid type 1 errors = high α

54 Different Decision Makers Disease Care Professional Clinician Health and Prevention Consumer

55 Health s Practitioners The ultimate decision makers of the practice of diet and health: INDIVIDUAL CONSUMERS

56 We are ignorant in a Hostile Environment

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