78-John Chang PresentationMedical device efforts using micro power

ultra wide band impulse radar (MUIR)

Medical sensing capabilities, help in battlefields and disaster zones

Electromagnetic sensor, sends pulse looks for echoes
Find people buried in rubble
Find brain issues too, subdural hematoma
Voice recognition
Low power, safe, non-ionizing, non-invasive, portable, cheap

Alexander J Malkin- Probing the architecture assembly and structure

function relationships of bio systems

Need for high res images of spores and viruses

Limited by ability to crystalize whatever you want to image
AFM- in vitro studies of high res architecture, assembly and proteomic
structure
o Atomic Force Microscopy
Evolution of bacterial cell life cycle- requires understanding of spore
coat high res architecture
Species can have different types of spore coverings- rodlet structures
common
Spore coat assembly controlled by nucleation/ crystallization conditions
o Macromolecular arrangement dependent upon chemical
environment and thermodynamic parameters
Spore coat formation good model for modeling cellular development
Germination process of C Novyi NT spores useful in cancer research
somehow
AFM got new info on how vaccinia virus structures form. Or something.
Structure-function relationships
Goal: cell wall architecture, composition, decomp dynamics.
o Converting biomass to liquid biofuel, costly and energy intensive
processing

Matthias Frank- Biological imagine with X-ray Free Electron Lasers

High res pics of biomolecules, x-ray crystallography

Structure related to bio function
Structural biology
Mass spec, x-ray crystal, NMR, electron microscopy, electron
tomography
1895 roentgen discovers x-ray
1912 max von laue proved x-rays are waves
Braggs law of diffraction
X-ray shows structure but can be damaging
 Phase problem- take a pic of x-ray and you dont have both amplitude
and phase in pic
o Phase must be obtained or est. separately
X-ray damage limits detail
Membrane structures still unknown
Standford Linear Accelerator Center (SLAC)
3km long, used in particle physics
Nano/ micro crystallography using LCLS- stepping stone towards single
molecule imaging
Coherent x ray imaging instrument- allows for high resolutions
CXDI ^ helps overcome radiation damage limitation
o Near atomic resolution achieved
Future: femtosecond x ray crystallography
o Single particle imaging

John Knezovich- LLNL overview

E.O. Lawrence, Edward Teller

1952
Nuclear weapons
National security, experimental and computational capabilities
Lots of NERDSSS
Many PHDS- 47% of employees
Most postdocs there end up full time career employees.
Fastest sequoia computer
CMAS- center for acc mass spec
Nustar deploys focusing telescopes to image the sky with high res x-
ray specs
o Census of collapses stars, black holes

Michael Malfatti- Biomedical Accelerator Mass Spec

Biosecurity, bioenergy, human health

AMS- mass spec-er analyzes ions at high energy, isotope ratios
Counts nuclei not decay events much faster / more efficient
Used since the 1990s (test body distribution and fate studies,
metabolism studies, molecular studies, and risk assessment)
Tests for environmental carcinogens
Ams allows for trace analysis of pharmacokinetics, metabolism,
macromol binding
Coupled to electrophoresis for drug binding of proteins
Quantifying metabolism = key to understand drug effects
Determining neuron turnover
AMS useful in dosing drug candidates
 o Microdosing- cheaper safer easier
Can correlate drug DNA damage and patient outcome for
chemotherapy
Limited by sample prep
Moving wire AMS- small molecules, macromoles
AMS
o Quantification of radioisotope compounds
o Platinum-DNA adducts caused by microdoses predict tumor
chemo response
Michael Thelen- Biotechnology for Biofuels

Biofuels- new source of energy, sustainable

CO2 bad for atomosphere
Lignocellulose biomass conversion viable alternative
o Sugarcane, canola, soy oil, algal lipids, switchgrass, sorghum,
poplar
Dept of Energy research centers- development of biofuels
Need to find more efficient way to process biomass for deconstruction
Cellulose purified using ionic liquids- high salt content
Many fuel producing organisms only use a fraction of sugar monomers
Pre treatment of biomass limits fuel production
Search rainforests for new enzymes and microbial things to help with
new biofuel production
o Green waste compost sites too
Green sequencing of metagenomes for new enzymes
o Look at DNA of microbes at feedsites- turtle grass, mangroves,
salt flats
Search for ionic liquid tolerance gene
New enzymes found that can depolymerize lignin
Problems of ionic liquid pretreatment
o More tolerant enzymes needed
o Genes to engineer microbial resistance
Alcohols, esters, alkanes to replace gas??
Microbes and synth bio helps to engineer new fuels, process-tolerant
strains
Cellulosic biofuels only viable alternative to oil/ gas.
Ionic liquids excellent cellulosic solvents, but inhibit biofuel
producing microbes
Bio refinery can deconstruct biomass and produce complex
hydrocarbons= fuel
Ionic liquid tolerance discovered in rainforest bacteria.
Metagenomics used to understand metabolic pathway of
lignocellulose degradation
Bill Colston- An Entrepreneurs Journey

Seed round founding- 1.4 Mil

o A round- 8.6 mill, B round 15 million
Digitize PCR
Sold to Biorad
Perseverance
Comm skills
Capacity for risk
Decision making
Mentors
Experience
Passion
Strategy
Vision
Recruiting top talent
2nd company- 2012- healthtell- snapshot of an immune system

Amy Rasley- Nanolipoprotein Particles- Vaccines

Goals
o Develop a flexible nanolipoprotien particle vaccine
Biodefense- pathogens continually evolving to elude host immunity
Anthrax, smallpox, plague, botulism, viruses- cat A bio threats
Vaccines- stimulate immune response without causing disease
Vaccine types
o Live organisms weakened (attenuated) chicken pox
o Inactive viruses- polio
o Toxoid vaccines- based on toxins secreted by pathogens- tetanus
o Subunit vaccines- pieces of pathogens- hepatitis
NLPs- animal modeling- can be customized for vaccines, therapeutics,
certain bio responses
Proteins, peptides, oligonucleotides, carbs, small organic compounds
all conjugated to NLPs
o Antigens and adjuvants can be incorporated into an NLP too
Delivery of antigens/ adjuvants using NLPs enhances systemic
generation of antibodies
Biothrax- anthrax vaccines
NLPs can be stored for a long time in cold storage, easily produced in a
factory too
NLPs good for customized treatment- antibody and adjuvant
delivery

Tom Slezak- biodefense, public health

 BioWatch
Comprehensive pathogen detection microarray
Threats- bacteria, viruses, fungi yeasts parasites, toxins, proteins
KPATH- DNA signature development system
Biowatch devices on the streets monitoring air
Prediction of H1N1 swine flu virulence
Microarrays allow for precise detection of specific short regions of DNA
LLMDA used for vaccine safety determination
o Also wound microbes
o Early detection/ diagnoses of cancers from pathogens
Predictive model for battlefield healing
Importance of bioinformatics and computer systems in
research

Hannah Farquar Tech transfer at LLNL

Process of taking knowledge from federal RD to private companies

Commercialization of scientific discovery
Chromosome painting- highest grossing license
Microdrop PCR
Safetrace- traces food?
Research is done for mission-focused work at LLNL.
Intellectual property is protected.
The IP is made available to the private sector.
Contractual relationship with a commercialization partner is achieved.
Revenue is generated for the company and the laboratory.
Lab-Corps: Leading lab scientists through the all-important customer
discovery process to validate the market potential of their technology;
based on iCorps/Steve Blank Lean Launchpad
Lab Accelerator: A new program led by LLNL that builds on Lab-Corps;
now that the customer discovery is done, well find business mentors
to mentor scientists and entrepreneurs through the startup creation
phase and then give them an opportunity to present shark tank style
to our network of investors.
Small Business Voucher (SBV): Department of Energy providing funding
for national lab scientists to perform applied research with market
information and specifications from an industrial partner.

Bioterrorism

Bacteria, fungi, viruses, toxins. From living orgs

Small pox- used as a purposeful plague thing. Blankets
WWI- anthrax and glanders in mules, anthrax in sugar cubes
Geneva convention bans use of bioweapons, not possession though
 Japan unit 731- did really really bad stuff. Killed over 200k Chinese for
experiments
Ww2- germans do stuff with rickets
uS does some testing with bio warfare,
USAMRIID- 69
1972- RISE- semi skilled biologist and nutbag try to poison water
supply
78- Bulgarian guy killed with ricin
79- anthrax hits soviets
91- weaponized anthrax, aflatoxin in gulf war
95- Tokyo- sarin gas
2001- anthrax in mail in US