Table 1: Fluorescence Quantitative (Excitation: 485nm/ Emission: 528nm) and optical dentity (600nm) Measurement of our Iron QS system under Iron rich and iron depleted medium. Culture under each condition is measured with three sample, and average value and standard deviation is calculated.
Blank
Sample1
Sample2
Sample3
AVG
SD
RFV
947652
960382
948677
952237
OD
0.591
0.628
0.593
0.604
RFV/OD
1603472.081
1529270.7
1599792.58
1577511.787
34144.6581
Iron QS+DP
AVG
RFV
391548
401613
398010
398010
OD
0.123
0.117
0.116
0.119
RFV/OD
3183317.073
3432589.74
3431120.69
3349009.169
117163.5394
Iron QS+FeSO4
AVG
RFV
545133
565243
552435
554270
OD
0.341
0.344
0.345
0.343
RFV/OD
1598630.499
1643148.26
1601260.87
1614379.612
20394.17861
Table 2: Summarize of the result of Fluorescence Quantitative (Excitation: 485nm/ Emission: 528nm) and optical dentity (600nm) Measurement of our Iron QS system under Iron rich and iron depleted medium.
Blank
Iron QS+DP
Iron QS
RFV(AVG)
952237
397057
554270
OD(AVG)
0.604
0.119
0.343
RFV/OD600
1576551.325
3345985.955
1614379.612
Figure 1- Relative fluorescence values of BL21 cell containing ironQS system after cultured in iron-rich and iron-limited media respectively. The Blank strain was set as controls.
Conclusion:
From the figure we can see that There's a significant difference of expression between iron-free and iron-rich environment. BL21-Iron QS has the highest expression of GFP when adding DP-under low concentration of ferric iron. The expression level between BL21-Iron QS in high Fe concentration medium and blank BL21 is similar, indicating that there's no GFP being expressed in both culture. FUR cannot bind to fur box and repress expression when Fe concentration is low is the medium, and vice versa. In our system, GFP can be expressed efficiently when Fe concentration is low.
Reference
1.Teng Chu, Chunshan Ni, Lingzhi Zhang, Qiyao Wang, Jingfan Xiao, Yuanxing Zhang ,and Qin Liu, A quorum sensing-based in vivo expression system and its application in multivalent bacterial vaccine, Microbial Cell Factories, DOI 10.1186/s12934-015-0213-9
SDS-Page
Figure 2: SDS-PAGE result of Iron-QS system expressing ORF 81.The antigen ORF81 with the poly His tag we constructed has a mass of 29 kDa. Lane 1, 2, and 3 are sample from high cell density, and lane 4, 5, 6 are sample from low cell density culture. As the result of SDS-page indicated, all six lanes share similar peptite band but different staining intensity, and there's presence of protein that is near 25 kDa for all six lanes. This pattern suggests that both culture are induced and the difference in staining intensity is a result of different cell density, so it's still not clear whether it's our protein of interest.
Western Blotting
Figure 3: Western blotting result of Iron-QS system expressing ORF 81. Lane 1, 2, and 3 are three repititions of sample A, and lane 4, 5, 6 are three repititions of sample B. As the result of western blotting indicated, three lanes of sample A share the same polypeptite band, so do three lanes of sample B. This suggests a difference in protein expression between sample A and B, which is a result of induction and repression of our system. Iron QS in sample A is ideally expressed as the iron chelator-DP-reduce the ferric iron concentration in the medium. The sytem in sample B is repressed by iron-bound holo FUR. However, three possible bands for protein of interest corresponds to 43 kDa molecular on the ladder. Although there's a difference between the result of western blotting and our ideal protein size (29 kDa), this might be caused by post translational modification of protein. Possible chemical modification, such as glycosylation, methylation, and phosphorylation, may contribute to the variance of protein size. Most membrane-bound proteins expressed in the endoplasmic reticulum are glycosylated, which entail covalent addition of sugar moieties to specific amino acids, to some extent [1]. Because the oligosaccharides could be very large, it's possible the bands are results of glycosylation of our protein of interest.
Figure 4: Example of different types of Glycosylation (From ThermoFisher)
OxyR (Old Part Characterization)
Table1. Fluorescence Quantitative (Excitation: 485nm/ Emission: 528nm) and optical dentity (600nm) Measurement of sample A, with the original OxyR transcription factor (BBa_K1104201) and OxyR induced promoter TrxCp (BBa_K1104201) from iGEM13_NYMU-Taipei under six H2O2 concentration (5mM, 2.5mM, 1mM, 0.1mM, 0.01mM,and 0mM). Culture under each concentration is measured with three sample, and average value and standard deviation is calculated.
H2O2 (mM)
Average
SD
5
RFV
567236
575491
568431
570386
OD600
0.22
0.24
0.221
0.227
RFV/OD
2578345.45
2397879.1
2572085.97
2516103.53
83636.2982
2.5
RFV
583944
586687
580442
583691
OD600
0.195
0.212
0.205
0.204
RFV/OD
2994584.61
2767391.5
2831424.39
2864466.83
95648.7650
1
RFV
945200
975187
954601
958329.333
OD600
0.31
0.312
0.323
0.315
RFV/OD
3049032.25
3125599.3
2955421.05
3043350.89
69591.0552
0.1
RFV
450025
449077
448871
449324.333
OD600
0.302
0.299
0.294
0.29833333
RFV/OD
1490149.00
1501929.7
1526772.10
1506283.62
15264.9923
0.01
RFV
303234
307976
308938
306716
OD600
0.341
0.338
0.338
0.339
RFV/OD
889249.266
911171.59
914017.751
904812.872
11066.3002
0
RFV
180294
183250
183005
182183
OD600
0.183
0.184
0.19
0.18566666
RFV/OD
985213.114
995923.91
963184.210
981440.412
13629.5509
Table2. Fluorescence Quantitative (Excitation: 485nm/ Emission: 528nm) and optical dentity (600nm) Measurement Blank BL21 culture under six H2O2 concentration (5mM, 2.5mM, 1mM, 0.1mM, 0.01mM,and 0mM). Culture under each concentration is measured with three sample, and average value and standard deviation is calculated.
H2O2 (mM)
Average
SD
5
RFV
488242
OD600
0.648
RFV/OD
753459.8765
49720
2.5
RFV
456371
OD600
0.585
RFV/OD
780121.3675
38567
1
RFV
499338.5
OD600
0.612
RFV/OD
815912.5817
30909
0.1
RFV
481699
OD600
0.573
RFV/OD
840661.4311
36491
0.01
RFV
468741
OD600
0.586
RFV/OD
799899.3174
49183
0
RFV
473121.5
OD600
0.599
RFV/OD
789852.2538
67900
Figure 5: Characterization of OxyR (BBa_K1104200) and TrxCp (BBa_K1104201). Comparision of relative fluorescence value (RFV)/OD600 of Sample A, with the original OxyR transcription factor (BBa_K1104200) from iGEM13_NYMU-Taipeiunder and OxyR induced promoter TrxCp (BBa_K1104201), and Blank, unmodifeid the BL21 E. coli, under six H2O2 concentration. Results indicate a significant difference between Sample A and Blank in all concentratio chosed.
OxyR Mutation (Improvement)
Table 3. Fluorescence Quantitative (Excitation: 485nm/ Emission: 528nm) and optical dentity (600nm) Measurement of sample B, with our modified OxyR (BBa_K3031018) and original promoter TrxCp (BBa_K1104201), under six H2O2 concentration (5mM, 2.5mM, 1mM, 0.1mM, 0.01mM,and 0mM). Culture under each concentration is measured with three sample, and average value and standard deviation is calculated.
H2O2 (mM)
Average
SD
5
RFV
567236
575491
568431
570386
OD600
0.22
0.24
0.221
0.227
RFV/OD
2578345.45
2397879.1
2572085.97
2516103.53
83636.2982
2.5
RFV
583944
586687
580442
583691
OD600
0.195
0.212
0.205
0.204
RFV/OD
2994584.61
2767391.5
2831424.39
2864466.83
95648.7650
1
RFV
945200
975187
954601
958329.333
OD600
0.31
0.312
0.323
0.315
RFV/OD
3049032.25
3125599.3
2955421.05
3043350.89
69591.0552
0.1
RFV
450025
449077
448871
449324.333
OD600
0.302
0.299
0.294
0.29833333
RFV/OD
1490149.00
1501929.7
1526772.10
1506283.62
15264.9923
0.01
RFV
303234
307976
308938
306716
OD600
0.341
0.338
0.338
0.339
RFV/OD
889249.266
911171.59
914017.751
904812.872
11066.3002
0
RFV
180294
183250
183005
182183
OD600
0.183
0.184
0.19
0.18566666
RFV/OD
985213.114
995923.91
963184.210
981440.412
13629.5509
Table 1: Fluorescence Quantitative (Excitation: 485nm/ Emission: 528nm) and optical dentity (600nm) Measurement of sample A, with the original OxyR transcription factor (BBa_K1104201) and OxyR induced promoter TrxCp (BBa_K1104201) from iGEM13_NYMU-Taipei under six H2O2 concentration (5mM, 2.5mM, 1mM, 0.1mM, 0.01mM,and 0mM). Culture under each concentration is measured with three sample, and average value and standard deviation is calculated.
H2O2 (mM)
Average
SD
5
RFV
360739
360956
342911
354868.6667
OD600
0.22
0.23
0.19
0.213333333
RFV/OD
1639722.727
1569373.913
1804794.7
1671297.126
170344
2.5
RFV
484957
476730
475935
479207.3333
OD600
0.236
0.241
0.247
0.241333333
RFV/OD
2054902.542
1978132.78
1926862.3
1986632.557
52616.5847
1
RFV
490687
473913
479366
481322
OD600
0.188
0.212
0.199
0.199666667
RFV/OD
2610037.234
2235438.679
2408874.3
2418116.762
153068.798
0.1
RFV
379381
380604
331979
363988
OD600
0.338
0.331
0.336
0.335
RFV/OD
1122428.994
1149861.027
988032.73
1086774.253
70713.2434
0.01
RFV
370919
361048
347991
359986
OD600
0.44
0.431
0.436
0.435666667
RFV/OD
842997.7273
837698.3759
798144.49
826280.1995
20012.2323
0
RFV
253738
243455
241936
246376.3333
OD600
0.275
0.295
0.289
0.286333333
RFV/OD
922683.6364
825271.1864
837148.78
861701.2039
43392.8731
Table 2. Fluorescence Quantitative (Excitation: 485nm/ Emission: 528nm) and optical dentity (600nm) Measurement Blank BL21 culture under six H2O2 concentration (5mM, 2.5mM, 1mM, 0.1mM, 0.01mM,and 0mM). Culture under each concentration is measured with three sample, and average value and standard deviation is calculated.
Figure 6: Our Improved OxyR (BBa_K3031018) oxidative stress sensitivity test comparing to original OxyR transcription factor (BBa_K1104200) from iGEM13_NYMU-Taipeiunder. Sample A is culture with the original OxyR transcription factor (BBa_K1104200) from iGEM13_NYMU-Taipeiunder and OxyR induced promoter TrxCp (BBa_K1104201); Sample B is replaced with our modified OxyR (BBa_K3031018) and Blank is just unmodifeid BL21 E. coli, under six H2O2 concentration. Results indicate a significant difference of relative fluorescence value (RFV)/OD600 between Sample A and Sample B in all concentrations tested, suggesting our modified OxyR does not show any significant improvement in the sensitivity toward H2O2 and has a decreased expression at higher concnetrations.
Future Direction
Since we do not have time to finish wet lab testing on cell wall anchoring system before Giant Jamboree with all finished design and ordered plasmid, we will finish the experiment and collect quantitative data in the future. Also, we may test the effect of out engineered system on living koi fish with a way without any ethical issue.
References:
Wormald, Mark R., Petrescu, Andrei J., Pao, Ya-Lan, Glithero, Ann, Elliott, Tim, & Dwek, Raymond A. (2002). Conformational studies of oligosaccharides and glycopeptides: Complementarity of NMR, X-ray crystallography, and molecular modelling.(Glycobiology). Chemical Reviews,102(2), 371-386.