Biological based Biosensor ’ s Inception

As an incipit, one has to define the term biosensor. The term has been enclosing several views and concepts, which we will not review here. Nevertheless, biological based biosensors can be common only defined as biological items, whose properties modifications upon environmental modifications can be measured. Herein this opinion article we will refer only to biosensors as the biological based ones, which cover [1] molecules : among the best characterized biosensors are the FRET (Förster Resonance Energy Transfer)-based, genetically encoded Kinase Activity Reporter (KAR) [1,2], (2) cells : CBB (Cells Based Biosensors; [3] and (3) organisms, like Xenopus embryos, whose development is sensitive to external factors (FETAX), Frog Embryo Teratogenesis Assay Xenopus [4] (Figure 1A).


Opinion
As an incipit, one has to define the term biosensor.The term has been enclosing several views and concepts, which we will not review here.Nevertheless, biological based biosensors can be common only defined as biological items, whose properties modifications upon environmental modifications can be measured.Herein this opinion article we will refer only to biosensors as the biological based ones, which cover [1] molecules : among the best characterized biosensors are the FRET (Förster Resonance Energy Transfer)-based, genetically encoded Kinase Activity Reporter (KAR) [1,2], (2) cells : CBB (Cells Based Biosensors; [3] and (3) organisms, like Xenopus embryos, whose development is sensitive to external factors (FETAX), Frog Embryo Teratogenesis Assay Xenopus [4] (Figure 1A).
The untangling of complex signalling network is imperative both for understanding cells and organisms physiological and pathological contexts, and for isolating the ideal property modifications to measure that will reflect, for example, the deregulation of these networks.These modifications are the one seeked for biosensors design or choice.Then, biosensors become mandatory for deciphering and characterizing molecular signatures associated with pathologies.The latter aspect is naturally tightly linked to prognosis and diagnosis.

Hub & Interplay
It is more or less consensual to assert that there are only a few molecules that can be taken as valuable for diagnosis, or to be considered as relevant for a signalling network's behaviour.Determining the ideal candidate for biosensors might be achieved, at the molecular level, by focusing on specific protein kinases or second messengers, which act as main effectors or contributors in many pathological contexts, like those which serve as converging hub or nodes for oncogenes.Among case-school enzymes are Protein Kinase A (PKA) [2] or Mitogen Activated Protein Kinases (MAPK) [5].
Nevertheless, is sensing one molecule for enzymatic activity enough?Indeed, network can be regulated by a plethora of post-translational modifications.The latter being able to impact each other in, for example, à yin-yang manner(O-GlcNAcversus phosphorylation [6], sulfhydration-nitrosylation [7].Initial studies focused on one enzymatic activity, upon modification by canonical regulators.Still, one has to keep in mind that a single enzymatic activity can be impacted by several post-translational modifications or yin yang balance.Main difficulty of this aspect is to anticipate the effects of combination and to seek for non-canonical pathways.As an example, preliminary studies enabled us to highlight the interplay between O-GlcNAc and phosphorylation on the regulation of the MAPK pathway, as seen by biosensors (Figure 1B).The latter has also been anticipated through classical approaches [8], but biosensing will provide a dynamical cell-by-cell view of this process.

Matriochka: the biosensor within the biosensor?
To get beyond the molecular aspects and its single angled focus, one can take advantage of the biosensors diversity, as abovementioned, and compatibility.The family of the biologically based biosensors is quite large, multiscale, but molecular biosensors might be integrated in cells or embryos, being themselves used as biosensing elements of their environment.Difficulties at this level +330320436867; E-mail: JeanFrancois.Bodart@univ-lille1.fr
are no longer technical.Many molecular biosensors have been successfully expressed and measured in various physiological environments, but not in the perspective to use both molecular and cells or organisms hosting them as biosensors.In such way, one might access to a more complete fingerprint and integrated signature of physiological or path physiological contexts.An added benefit of biosensors towards -omics approaches remain in their intrinsic ability to measure dynamic processes and not to provide single snapshots.

Figure 1 :
Figure 1: Biological biosensors.A) Scheme of the different biosensors scales, ranging from molecules (genetically encoded biosensor), cells and oocytes (CBB) to embryo.B) Representative MAPK activity measurement in living cell after maximum MAPK activation and OGA inhibition (Thiamet G) the reduced O-GlcN Acylation level induces a reduced MAPK activity.Images represent MAPK activity in cell nucleus between 0 and 30mn (picture size 12µm, the hottest colours correspond to the highest activity).For details about acquisition and analysis procedure, see[1,2].