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Engineering Aspects of Bioluminescence Resonance Energy Transfer Systems

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Engineering in Translational Medicine

Abstract

Development of optical probes for sensing biological functions in vivo is in high demand in modern biology. With several inherent advantages, the bioluminescence resonance energy transfer (BRET)-based sensors are rapidly expanding and showing great utilities in the study of protein–protein interactions (PPIs), protein dimerization, signal transduction, etc. Since its inception in the late nineties, BRET-related research has gained significant momentum in terms of adding versatility to the assay format and wider applicability where it has been suitably used. Beyond the scope of quantitative measurement of PPIs and protein dimerization, molecular imaging applications based on BRET assays have broadened its scope for screening pharmacologically important compounds by in vivo imaging and high-throughput screening (HTS) methods. Taking examples from literatures, this chapter will contribute to an in-depth knowledge on engineering requirements of BRET components such as donor, acceptor, substrate chemistry, and instrumentations. BRET applications having significant contributions toward making it an attractive single-format assay are also discussed.

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Abbreviations

PPI/PPIs:

Protein–protein interaction(s)

ELISA:

Enzyme-linked Immunosorbent Assay

Y2H:

Yeast two-hybrid assay

IY2H:

Induced Yeast two-hybrid assay

PCAs:

Protein-fragment complementation assays

FRET:

Fluorescence resonance energy transfer

BRET:

Bioluminescence resonance energy transfer

BL:

Bioluminescence

RLuc:

Renilla luciferase

FLuc:

Firefly luciferase

ATP:

Adenosine triphosphate

LH2 :

D-Luciferin substrate for FLuc

AMP:

Adenosine monophosphate

CO2 :

Carbon dioxide

Emmax :

Emission maximum

Clz:

Coelenterazine

RET:

Resonance energy transfer

ERET :

Efficiency of resonance energy transfer

FP/FPs:

Fluorescent protein(s)

GFP:

Green fluorescent protein

EYFP:

Enhanced yellow fluorescent protein

Exmax :

Excitation maximum

Cf :

Correction factor

Clz-h :

Coelenterazine-h

RFP:

Red fluorescent protein

Clz-v :

Coelenterazine-v

CBP:

Coelenterazine-binding protein

RLuc-m:

Renilla muelleri luciferase

BLI:

Bioluminescence imaging

MLuc:

Metridia luciferase

OLuc:

Oplophorus luciferase

CBG:

Click beetle green luciferase

GLuc:

Gaussia luciferase

VLuc:

Vargula luciferase

NLuc:

NanoLuc™

OLuc-19:

19-kDa catalytic domain of OLuc

OLuc-35:

35-kDa stabilizing domain of OLuc

wtGFP:

Wild-type green fluorescent protein

avGFP:

Green fluorescent protein from Aequorea victoria

EGFP:

Enhanced green fluorescent protein

RFP:

Red fluorescent protein

SRET:

Sequential resonance energy transfer

BiFC-BRET:

Bimolecular fluorescence complementation-bioluminescence resonance energy transfer

CODA-RET:

Complemented donor–acceptor resonance energy transfer

BiLC-BiFC:

Bimolecular luminescence complementation-bimolecular fluorescence complementation

NST:

Nocistatin

N/OFQ:

Nociceptin/Orphanin FQ

HIV:

Human immunodeficiency virus

PR:

Protease

HTS:

High-throughput screening

FCV:

Feline calicivirus

RG:

Arginine–glycine peptide

CRET:

Chemiluminescence resonance energy transfer

tdTA:

tdTomato-aequorin system

CaM:

Calmodulin

cpVenus:

Circularly permuted Venus

cpFPs:

Circularly permuted fluorescent proteins

FKBP12:

FK506-binding protein 12

FRB:

FKBP12-Rapamycin-binding domain

mTOR:

Mammalian target of rapamycin

GPCR:

G protein-coupled receptor

CB1R:

Cannabinoid-1 receptor

D2R:

Dopamine D2 receptor

A2AR:

Adenosine A2A receptor

SH2:

Src homology 2 domain

OS-BLIA:

Open sandwich bioluminescent assay

VH :

Variable heavy chain of antibody

VL :

Variable light chain of antibody

Trx:

Thioredoxin

RT-PCR:

Reverse-transcriptase polymerase chain reaction

ARM:

Arginine-rich motifs

BIV:

Bovine immunodeficiency virus

JDV:

Jembrana deficiency virus

NIR:

Near-infrared

QD/QDs:

Quantum dot(s)

MMP-2:

Matrix metalloproteinase-2

MMP-7:

Matrix metalloproteinase-7

uPA:

Urokinase-type plasminogen activator

CLuc:

Cypridina luciferase

FBP:

Far-red bioluminescent protein

Dlk-1:

Delta-like protein-1

C-60:

Carbon-60/Fullerene

PMT:

Photomultiplier tube

BLM:

Bioluminescence microscopy

CCD:

Charge-coupled device

EB-CCD:

Electron bombarded charged coupled device

EMCCD:

Electron multiplying cooled charge-coupled

DR:

Double ratio

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Acknowledgments

Funding support to AD from DBT Bioengineering, New Delhi and ACTREC, TMC, India is gratefully acknowledged.

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  1. Molecular Functional Imaging Lab, ACTREC, Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai, Maharashtra, 410210, India

    Abhijit De, Rohit Arora & Akshi Jasani

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  1. Abhijit De
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  1. Dept of Radiology/Medical Physics/Biomed, University of Wisconsin, Madison, USA

    Weibo Cai

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De, A., Arora, R., Jasani, A. (2014). Engineering Aspects of Bioluminescence Resonance Energy Transfer Systems. In: Cai, W. (eds) Engineering in Translational Medicine. Springer, London. https://doi.org/10.1007/978-1-4471-4372-7_10

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