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Library Growth

Protocol for Library Growth with LB Media

Introduction

This protocol outlines the steps to grow up your libraries and perform chemical genomics for sequence quantification.

Materials

  • Library
  • Culture tubes
  • Eppitubes
  • LB (Luria-Bertani) media
  • 250 mL flasks
  • PCR tubes
  • Falcon tubes

Procedure

Competition Fitness Assay with Chemicals

Prep

  1. Assign Alphanumeric Labels: Assign alphanumeric labels for each sample and print out a "cheat sheet."
  2. Calculate Dilutions for IPTG:
    • Volume of IPTG to add = (Final Volume of Culture / 1000)
    • Note: The dilution factor for IPTG is 1000 (from 1M to 1mM).
  3. Prep 250 mL Flasks: Prepare 250 mL flasks for T0 collections.
  4. Label Eppitubes: Prep Eppitubes with labels for pellet collection.

Day 1

  1. Inoculate Flask: In a 250 mL flask, add 35 mL LB. To achieve a starting OD of 0.02, use the following volumes based on the stock OD:
    • For E. coli with stock OD = 25: Use 28 uL
    • For E. cloacae with stock OD = 30: Use 23 uL
    • For K. pneumoniae with stock OD = 30: Use 23 uL
    • Equation: Volume to inoculate = (Desired OD x Culture Volume) / Stock OD
  2. Incubate: Place the flask in a 37°C shaker until the OD reaches 0.2.
  3. Collect T0 Samples: Take 10 mL from each flask and distribute into Falcon tubes for each of the 3 replicates, including a backup for each. Note: 10 mL at OD 0.2 is approximately equivalent to 1 mL at OD 2.
  4. Prep for DNA Extraction: Utilize the entire pellet for DNA extraction.
  5. Prep Overnight Tubes for T1: Inoculate another overnight tube with 1 mL from the Falcon tube to achieve a starting OD of 0.02.
  6. Incubate Tubes: Place tubes in a tube rack and incubate in a 37°C shaker for 18 hours.

Day 2 and Beyond

  1. Measure OD: After 18 hours of incubation, extract 100 uL from each T1 tube. Dilute this into 900 uL of LB for a 1:10 dilution and measure the OD.
  2. Prep for DNA Extraction: Take 1 mL, spin down, and store for DNA extraction. Take an additional 1 mL as a backup.
  3. Prep for Next Timepoint (Tn): Inoculate another overnight tube with the aim of reaching an OD of 0.02 in 4 mL. Use 40 uL from the previous overnight.
  4. Incubate Tubes: Place tubes in a 37°C shaker for 18 hours.

Repeat steps 1-4 for each subsequent day until you are done with the experiment.

@ryandward
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ryandward commented Sep 16, 2023

Attempt 1 - September 14-16, 2023 (E. coli induction only)

Failure: Inoculated at too low of a dilution (4uL instead of 40uL during passages)

Sample Organism Strain IPTG Actual OD600
T0(1) E. coli 5142 0 0.216
T0(2) E. coli 5142 0 0.209
T0(3) E. coli 5142 0 0.218

September 15, 2023 - 2:10 PM (T1)

  • Time Passed: 19.5 hours from T0
Sample Organism Strain IPTG Diluted OD600 Actual OD600
T1(1) E. coli 5142 0 0.232 2.32
T1(2) E. coli 5142 0 0.275 2.75
T1(3) E. coli 5142 0 0.2 2.0
T1(1) E. coli 5142 1mM 0.278 2.78
T1(2) E. coli 5142 1mM 0.212 2.12
T1(3) E. coli 5142 1mM 0.336 3.36

September 16, 2023 - 10:10 AM (T2)

  • Time Passed: 20 hours from T1
Sample Organism Strain IPTG Diluted OD600 Actual OD600
T2(1) E. coli 5142 0 0.202 2.02
T2(2) E. coli 5142 0 0.278 2.78
T2(3) E. coli 5142 0 0.262 2.62
T2(1) E. coli 5142 1mM 0.287 2.87
T2(2) E. coli 5142 1mM 0.261 2.61
T2(3) E. coli 5142 1mM 0.326 3.26

Here, I realized I was inoculating at too low of an inoculum. I was diluting 1:1000, with 4uL.

Redo with appropriate dilution of 1:100, with 40 uL.

@ryandward
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ryandward commented Sep 22, 2023

Attempt 2 - September 17-19, 2023 (E. coli induction only)

Failure: Sulfur smell and unequal ODs

Note: The aim is to inoculate cultures at an OD600 of 0.02.

Day 1 - T0 Prep (September 17, 2023)

  • Used 3 flasks of 250 mL size.
  • In each flask, added 40 mL LB and 28 uL E. coli library (OD600 = 25).

T0 In and T0 Out OD600 Measurements

Date Stage Time Flask OD600
Sep 17, 2023 T0 In 3:33 PM A 0.025
Sep 17, 2023 T0 In 3:33 PM B 0.024
Sep 17, 2023 T0 In 3:33 PM C 0.028
Sep 17, 2023 T0 Out 5:23 PM A 0.234
Sep 17, 2023 T0 Out 5:23 PM B 0.233
Sep 17, 2023 T0 Out 5:23 PM C 0.242

Dilution and Induction (September 18, 2023)

  • Diluted 400 uL culture into 3600 uL LB or LB+IPTG (1mM IPTG).

T1 In and T1 Out OD600 Measurements

Date Stage Time Flask OD600 Induction
Sep 17, 2023 T1 In 5:33 PM 1A 1:10 dilution -IPTG
Sep 17, 2023 T1 In 5:33 PM 1B 1:10 dilution -IPTG
Sep 17, 2023 T1 In 5:33 PM 1C 1:10 dilution -IPTG
Sep 17, 2023 T1 In 5:33 PM 1D 1:10 dilution +IPTG
Sep 17, 2023 T1 In 5:33 PM 1E 1:10 dilution +IPTG
Sep 17, 2023 T1 In 5:33 PM 1F 1:10 dilution +IPTG
Sep 18, 2023 T1 Out 11:30 AM 1A 2.77 -IPTG
Sep 18, 2023 T1 Out 11:30 AM 1B 2.52 -IPTG
Sep 18, 2023 T1 Out 11:30 AM 1C 2.41 -IPTG
Sep 18, 2023 T1 Out 11:30 AM 1D 2.52 +IPTG
Sep 18, 2023 T1 Out 11:30 AM 1E 2.47 +IPTG
Sep 18, 2023 T1 Out 11:30 AM 1F 2.58 +IPTG

T2 In and T2 Out (September 18-19, 2023)

  • Diluted 40 uL culture into 4 mL LB or LB+IPTG.
  • T2 In at 11:40 AM on September 18th and T2 Out at 5:33 AM on September 19th.

T2 In and T2 Out OD600 Measurements

Date Stage Time Flask OD600 Induction
Sep 18, 2023 T2 In 11:40 AM 2A 1:100 dilution -IPTG
Sep 18, 2023 T2 In 11:40 AM 2B 1:100 dilution -IPTG
Sep 18, 2023 T2 In 11:40 AM 2C 1:100 dilution -IPTG
Sep 18, 2023 T2 In 11:40 AM 2D 1:100 dilution +IPTG
Sep 18, 2023 T2 In 11:40 AM 2E 1:100 dilution +IPTG
Sep 18, 2023 T2 In 11:40 AM 2F 1:100 dilution +IPTG
Sep 19, 2023 T2 Out 5:33 AM 2A 2.17 -IPTG
Sep 19, 2023 T2 Out 5:33 AM 2B 3.05 -IPTG
Sep 19, 2023 T2 Out 5:33 AM 2C 3.03 -IPTG
Sep 19, 2023 T2 Out 5:33 AM 2D 2.38 +IPTG
Sep 19, 2023 T2 Out 5:33 AM 2E 2.38 +IPTG
Sep 19, 2023 T2 Out 5:33 AM 2F 3.19 +IPTG

T3 In and T3 Out (September 19, 2023)

  • Diluted 3A-3F cultures by 1:100 (i.e., 40 uL into 4 mL LB or LB+IPTG).
  • T3 In at 5:43 AM and T3 Out at 10:30 PM on September 19th.

Note: Tube 3F had a sulfur-like smell.

T3 In and T3 Out OD600 Measurements

Date Stage Time Tube OD600 Induction
Sep 19, 2023 T3 In 5:43 AM 3A 1:100 dilution -IPTG
Sep 19, 2023 T3 In 5:43 AM 3B 1:100 dilution -IPTG
Sep 19, 2023 T3 In 5:43 AM 3C 1:100 dilution -IPTG
Sep 19, 2023 T3 In 5:43 AM 3D 1:100 dilution +IPTG
Sep 19, 2023 T3 In 5:43 AM 3E 1:100 dilution +IPTG
Sep 19, 2023 T3 In 5:43 AM 3F 1:100 dilution +IPTG
Sep 19, 2023 T3 Out 10:30 PM 3A 2.26 -IPTG
Sep 19, 2023 T3 Out 10:30 PM 3B 2.92 -IPTG
Sep 19, 2023 T3 Out 10:30 PM 3C 2.80 -IPTG
Sep 19, 2023 T3 Out 10:30 PM 3D 2.96 +IPTG
Sep 19, 2023 T3 Out 10:30 PM 3E 2.96 +IPTG
Sep 19, 2023 T3 Out 10:30 PM 3F 1.83 +IPTG

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ryandward commented Sep 22, 2023

✅ Attempt 3 - September 20-22, 2023 (E. coli induction only)

T0 In and T0 Out (September 20, 2023)

  • Inoculation aim is still at 0.02 OD600.
  • T0 In at 8:05 PM and T0 Out at 9:50 PM on September 20th.

T0 In and T0 Out OD600 Measurements

Date Stage Time Flask OD600 Induction
Sep 20, 2023 T0 In 8:05 PM 0A 0.017 -IPTG
Sep 20, 2023 T0 In 8:05 PM 0B 0.022 -IPTG
Sep 20, 2023 T0 In 8:05 PM 0C 0.019 -IPTG
Sep 20, 2023 T0 Out 9:50 PM 0A 0.217 -IPTG
Sep 20, 2023 T0 Out 9:50 PM 0B 0.214 -IPTG
Sep 20, 2023 T0 Out 9:50 PM 0C 0.221 -IPTG

T1 In and T1 Out (September 20-21, 2023)

  • Inoculation aim is still at 0.02 OD600.
  • Diluted 0A-0F cultures by 1:10 (i.e., 400 uL into 3.6 mL LB or LB+IPTG).
  • T1 In at 9:50 PM on September 20th and T1 Out at 4:10 PM on September 21st.

T1 In and T1 Out OD600 Measurements

Date Stage Time Tube OD600 Induction
Sep 20, 2023 T1 In 9:50 PM 1A 1:10 dilution -IPTG
Sep 20, 2023 T1 In 9:50 PM 1B 1:10 dilution -IPTG
Sep 20, 2023 T1 In 9:50 PM 1C 1:10 dilution -IPTG
Sep 20, 2023 T1 In 9:50 PM 1D 1:10 dilution +IPTG
Sep 20, 2023 T1 In 9:50 PM 1E 1:10 dilution +IPTG
Sep 20, 2023 T1 In 9:50 PM 1F 1:10 dilution +IPTG
Sep 21, 2023 T1 Out 4:10 PM 1A 2.92 -IPTG
Sep 21, 2023 T1 Out 4:10 PM 1B 2.78 -IPTG
Sep 21, 2023 T1 Out 4:10 PM 1C 2.90 -IPTG
Sep 21, 2023 T1 Out 4:10 PM 1D 2.92 +IPTG
Sep 21, 2023 T1 Out 4:10 PM 1E 2.98 +IPTG
Sep 21, 2023 T1 Out 4:10 PM 1F 2.95 +IPTG

T2 In and T2 Out (September 21-22, 2023)

  • Inoculation aim is still at 0.02 OD600.
  • Diluted 1A-1F cultures by 1:100 (i.e., 40 uL into 4 mL LB or LB+IPTG).
  • T2 In at 4:20 PM on September 21st and T2 Out at 11:10 AM on September 22nd.

T2 In and T2 Out OD600 Measurements

Date Stage Time Tube OD600 Induction
Sep 21, 2023 T2 In 4:20 PM 2A 1:100 dilution -IPTG
Sep 21, 2023 T2 In 4:20 PM 2B 1:100 dilution -IPTG
Sep 21, 2023 T2 In 4:20 PM 2C 1:100 dilution -IPTG
Sep 21, 2023 T2 In 4:20 PM 2D 1:100 dilution +IPTG
Sep 21, 2023 T2 In 4:20 PM 2E 1:100 dilution +IPTG
Sep 21, 2023 T2 In 4:20 PM 2F 1:100 dilution +IPTG
Sep 22, 2023 T2 Out 11:10 AM 2A 3.07 -IPTG
Sep 22, 2023 T2 Out 11:10 AM 2B 2.80 -IPTG
Sep 22, 2023 T2 Out 11:10 AM 2C 2.90 -IPTG
Sep 22, 2023 T2 Out 11:10 AM 2D 3.03 +IPTG
Sep 22, 2023 T2 Out 11:10 AM 2E 3.13 +IPTG
Sep 22, 2023 T2 Out 11:10 AM 2F 3.02 +IPTG

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