harnessing genomics for global health: evolving infectious ......sep 16, 2015 · malaria...
TRANSCRIPT
Harnessing Genomics for Global Health: Evolving Infectious Diseases
The Science of Malaria Eradication
Red Queen Dynamics: The evolutionary Arms race
“Well, in your country," said Alice panting a little, "you'd generally get to somewhere else - if you ran very fast for a long time, as we have been doing."
"A slow sort of country!" said the Red Queen. " Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!"
Lewis Carroll, Through the Looking Glass
Howard Markel and Stephen Doyle, New York Times (Op-Ed, April 30, 2003)
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Differential Diagnosis for Febrile Illness
Acute arthritis Persistent arthralgia
Pulmonary symptoms* Gastroenteritis‡
Polyuria, dysuria, sepsis** Cyclic fever†
Conjunctival/mucosal rash Jaundice◊
Purpura**
[Ab. Pain/Diarrhea] Headache Arthralgia Myalgia
Rash Fever
Hemorrhagic fever
Encephalitis
Dengue Chikungunya
Other pathogens Influenza*, measles*, Rubella*, EBV, Meningeococcal infection**, rotavirus‡, cholera, malaria†, leptospirosis◊, RFV, disseminated Gonococceal disease**, typhus.
Phenotype
Genome Scans
Loci Selection
GWAS
Assay Development
Application
Sample Collection
Sequence Validation
Genotyping
Pipeline—From Samples to Application
Malaria Eradication: An Audacious Goal
“Any goal short of eradicating malaria is accepting malaria; it’s making peace with malaria; it’s rich countries saying: ‘We don’t need to eradicate malaria around the world as long as we’ve eliminated malaria in our own countries. That's just unacceptable.” • Melinda Gates, 2007 • February 6, 2013_v7 © 2012 Bill & Melinda Gates Foundation | 4
Move to rapidly scale up diagnostics and sequencing
Equipment and Supplies Infrastructure Training
The impact of genomic surveillance
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Challenge in 2003 • Drugs for neglected diseases
• Old – discovered in the first half of 20th century • Limited therapeutic window • Unknown mechanism
• Missed the revolution in drug discovery • Science discovery and drug discovery uncoupled • Technology lagged • Fragmented efforts
DNA: the genetic
material 1944
DNA structure
1953 Genetic code 1966
Recombinant DNA 1972
DNA sequencing
1977
Genbank established
1982 PCR 1985
Human Genome Project 1990
Atavoquone 1951
Suramin 1921
Melarsapol 1949
Leap-frogging into 21st Century
• Genomic revolution • Genetic engineering of parasites • Whole genome sequencing
• New Chemical Entities identified • Success in developing assays • Success in High Throughput Screening (HTS) • Exploration of “chemical space”
• Combining genomics and chemistry • New target identification • RNAi identification of essential pathways
• Concerted scientific effort on problem of drug and vaccine discovery
DNA: the genetic
material 1944
DNA structure
1953 Genetic code 1966
Recombinant DNA 1972
DNA sequencing
1977
Genbank established
1982 PCR 1985
Human Genome Project 1990
Atavoquone 1951
Suramin 1921
Melarsapol 1949
HTS 1999
RNAi 2000
Genetically engineered
parasites 1990s
First genome 2002
Education and Leadership Training
Education and Leadership Training
• Study diseases in natural setting led by endemic scientists • Training and mutual learning with new goals • Technology is creating the opportunity for innovation
Defeating Malaria: From the Genes to the Globe
Stamp Out Malaria!
MANAGING A RESEARCH LABORATORY
Who and What constitutes a laboratory
Personnel
Equipment
Reagents
Infrastructure
Personnel
Laboratory Office
Designs and executes research
projects
Training required to comply with regulations
Provides administrative
support
Aware of regulation, maintains records
Equipment
Ordering/ Inventory
SOP
Training
Maintenance/ Disposal
Reagents..
Ordering/ Inventory
SOPS (CHP, EP)
Storage/disposal
Infrastructure
Basic (Air, Heat, Water)
Specialized (Vivarium, BSL2, BSL3, Insectary)
The Regulatory Landscape
Internal checks External checks
COMS
IACUC
IRB
EHS
RMAS
NIH
CDC
State/City
Accreditation bodies
AAALAC
USDA
Resources
ORARC
EHS
Operations
NIH OBA
AALAS
Guidance document
CDC, USDA
Internal External
Leadership Roles Responsibility
Expectations
Response Hierarchy
Principal Investigator
Laboratory Manager
Investigator/Buddy
Facility personnel Security Occupational Health EHS
PI Operation Director
Dean
Agents.. Plasmodium species::Malaria
HIV::AIDS
Mycobacterium species::Tuberculosis
Trypanosoma species:: Chagas Disease
Neisseria species:: Gonorrhea
Streptococcus species:: Pneumonia
Gut Bacteria:: IBD, Cancer
Vector Biology:: Mosquitoes
Laboratories…
BL3
BL2
BL1
Containment
PPE
Practice
The Risk Pyramid
ABL2 ACL2
ABL3