Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Beam Time Allocation

UC Berkeley25%

25%

25%10%

8%

5%

2%Plexxikon

General User Program

Staff

George Meigs

Senior Research Associate

James Holton

Beamline Director

Jane Tanamachi

Administrator

Tom Alber

Principal Investigator

PRT

Member Labs

PRT

Contractees

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Funding for ALS 8.3.1

FY 2006 cost Total cost End date

Contracts U Alberta $200,000 $800,000 01/07

MD Anderson $116,000 $748,000 07/08

Plexxikon $150,000 $1.25 M 02/07

UCSD $35,000 $145,000 2011

Grants UCSF NIH Center grant

$80,000 $320,000 6/10

DOE IDAT (SIBYLS) $84,000 TBD 9/09

NIH STTR (Fluidigm) $28,200 $141,000 7/08

Total $693,200 $3.4 M -

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

AD

SC

Qu

antu

m 2

10

X-ray opticsSuperbend

PlaneParabolic

mirror

Torroidalmirror

Si(111)monochromator

Protein Crystal

pinhole Scatterguard

• 2:1 demagnification cancels spherical aberrations

• comparable flux to a wiggler with < 1% of the heat

divergenceslits

AD

SC

Qu

antu

m 2

10

X-ray opticsSuperbend

PlaneParabolic

mirror

Torroidalmirror

Si(111)monochromator

Protein Crystal

pinhole Scatterguard

• 2:1 demagnification cancels spherical aberrations

• comparable flux to a wiggler with < 1% of the heat

divergenceslits

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Safety Management

• Hardware safety systems• Training• Safety through simplicity• Failsafe envelope

• Examples:– Liquid nitrogen – better tools– Automatic retraction – eliminate confusion– Automatic backup – eliminate distraction

Safety EnvelopeRadiation Safety System (RSS)

Personnel Protection System (PSS)

Equipment Protection System (EPS)

GERT Training 8.3.1 Training

experiment

Safety EnvelopeRadiation Safety System (RSS)

Personnel Protection System (PSS)

Equipment Protection System (EPS)

GERT Training 8.3.1 Training

experiment

Safety Envelope

“There is no safety system that can stop a determined user with a hacksaw”

-Anonymous

Solution:

Create tools that enhance productivity within the safety envelope

Example 1: Liquid nitrogen

Liquid nitrogen safety concern

A safer way

Safer and more productive!

Example 2: Automatic detector retraction

ADSC Quantum 210

ADSC Quantum 210

Detector retraction

ADSC Quantum 210

Detector retraction

Automatic detector retraction

• Detector motors are disabled with hutch door open (pinch hazard)

• Sample is difficult to access with detector in data collection position

• Common mistake: – forget to retract detector before opening door

• Result: confusion• Solution:

– Door will not open with detector forward– Detector automatically retracts on door open attempt

March 2003MOTOROLA and the Stylized M Logo are registered in the US

Patent & Trademark Office. All other product or service names are the property of their respective owners.

© Motorola, Inc. 2002.

Distraction is unsafe!Distraction is unsafe!

0.8

1.0

1.2

1.4

1.6

1.8

2 4 6 8

Distance from the lead vehicle (secs.)

Me

dia

n t

ime

to

lif

t fo

ot

off

ac

ce

lera

tor

(se

cs

.)

DistractionCondition

No-DistractionCondition

0.8

1.0

1.2

1.4

1.6

1.8

2 4 6 8

Distance from the lead vehicle (secs.)

Me

dia

n t

ime

to

lif

t fo

ot

off

ac

ce

lera

tor

(se

cs

.)

DistractionCondition

No-DistractionCondition

Drivers following a car that suddenly brakes take longer to respond to that event when they are distracted by trying to solve a logic problem. This is especially true if the two vehicles start out close together--when it is critical that the driver in the following vehicle make a rapid response to avoid a rear-end collision.

Automated firewire drive backup

Automated DVD archive

Safety Summary

• Encourage safe practices by making them the best way to get results

• Measures are in addition to existing ALS safety envelope

• Better science and better safety can go hand in hand

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Software

BLU-ICE 3.0 control system

Elves integrated with BLU-ICE

ALS-wide beamline health monitor

Touch screen

Integration of Elves with BLU-ICE

Elvesstructure solution

data collection

index

Wedger Elves

mosflmautoindexstrategy

most recent im

age

run information

Integration of Elves with BLU-ICE

Elvesstructure solution

data collection

process

run information

pickun-busyclusternode

mosflmscalasolve

ARP/wARP

Apr 6 – 24 at ALS 8.3.1

Elven Automation

27,686 images collected

148 datasets (15 MAD)

31 investigators

56 unique cells

5 KDa – 23 MDa asymmetric unit

0.94 – 32 Å resolution (3.2 Å)

Apr 6 – 24 at ALS 8.3.1

Elven Automation

148 datasets

117 succeded

~3.5 (0.1-75) hours

31 failed

~61 (0-231) hours

2 / 15 MAD structures

ALS beamline health monitor

ALS lN2 health monitor

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

Beamline 8.3.1

PRT organization

Funding

Hardware

Safety management

Control system

Scientific productivity

AmtB ammonia channel

Khademi et. al. (2004) Science 305 1587-94.

The E. coli ribosome

Schuwirth et. al. (2005) Science 310 827-34

DnaA origin-recognition protein

Erzberger et. al. (2006) Nat Struct Mol Biol 13, 676-83

E. coli rho

Skordalakes and Berger (2003) Cell 114, 135

multidrug transporter EmrD

Yin et. al. (2006) Science 312 741-4

How many are we solving?

Jiang & R.M. Sweet (2004)

Seconds Description Percent

104490 Assigned and available 91%

42093 Shutter open 40%

52684 Collecting (3026 images) 50%

51806 Something else 50%

Operational Efficiency“representative” 8.3.1 user

Number Description Percent

446028 Images (~7 TB) 33%

2346 Data sets 47%

449 MAD/SAD (1:2) 19%

48 Published 2%

8.3.1 in 2003

Turning data into models

Overlaps

Signal to noise

Radiation Damage

Why do structures fail?

Overlaps

Signal to noise

Radiation Damage

Why do structures fail?

Apr 6 – 24 at ALS 8.3.1

Elven Automation

148 datasets

117 succeded

~3.5 (0.1-75) hours

31 failed

~61 (0-231) hours

2 / 15 MAD structures

avoiding overlaps

c

c

Overlaps

Signal to noise

Radiation Damage

Why do structures fail?

Overlaps

Signal to noise

Radiation Damage

Why do structures fail?

Apr 6 – 24 at ALS 8.3.1

Elven Automation

148 datasets

117 succeded

~3.5 (0.1-75) hours

31 failed

~61 (0-231) hours

2 / 15 MAD structures

MAD phasing simulation

-0.2

0

0.2

0.4

0.6

0.8

1

0.01 0.1 1 10

Anomalous signal to noise ratio

Cor

rela

tion

coef

ficie

nt t

o co

rrec

t m

odel

mlphare results

Minimum required signal (MAD/SAD)

"#

)(3.1

fsitesDaMW

sd

I

Overlaps

Signal to noise

Radiation Damage

Why do structures fail?

Overlaps

Signal to noise

Radiation Damage

Why do structures fail?

thaw

Radiation Damage

Lattice damage

Distention of cryo with dose

before

beam

Distention of cryo with dose

after

beam

Specific Damage

Specific Damage

Individual atoms decay at different rates

00.10.20.30.40.50.60.70.80.9

1

0 20 40 60 80 100

all atoms

Se #1

Se #5

dose (MGy)

Cor

rela

tion

coef

ficie

nt t

o ob

serv

ed d

ata

0 12 24 36 48 60

fluorescence probe for damage

Absorbed Dose (MGy)

Fra

ctio

n u

nco

nve

rted

Wide range of decay rates seen

0.

0

0

.2

0.4

0.6

0

.8

1.0

0 50 100 150 200

Half-dose = 41.7 ± 4 MGy“GCN4” in crystal

Half-dose = 5.5 ± 0.6 MGy8 mM SeMet in NaOH

Protection factor: 660% ± 94%

How to improve productivity

• Nocturnal automation

• Offline experimental design

• Understand radiation damage

Interleaved Schedulingexperiment queue beamline

Minor 30s

Choe 120s

Alberta 60s

Alberta 60s

Choe 30s

Minor 30s

cool hand luke

“infinite capacity” sample carousel

6-foot conveyor