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The development of biological devices that transform living cells into biosensors, nano-factories, and therapeutic agents is the objective of synthetic biology. CeCyL is a university wide research laboratory interested in innovations that make such devices reliable and efficient enough to make the biological systems a generally useful technology.  We apply tools from engineering and synthetic biology to 1) build electromechanical devices co-designed with biological devices, 2) derive estimation and modeling methods specifically for biological systems, and 3) develop biological control mechanisms and theory.   
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The development of biological devices that transform living cells into biosensors, nano-factories, and therapeutic agents is the objective of synthetic biology. Georgiev Lab is a university wide research laboratory interested in innovations that make such devices reliable and efficient enough to make the biological systems a generally useful technology.  We apply tools from engineering and synthetic biology to 1) build electromechanical devices co-designed with biological devices, 2) derive estimation and modeling methods specifically for biological systems, and 3) develop biological control mechanisms and theory.   
  
 
If you are interested in joining us in this effort or if you are just simply interested, contact Dr. Daniel Georgiev (georgiev@kky.zcu.cz).
 
If you are interested in joining us in this effort or if you are just simply interested, contact Dr. Daniel Georgiev (georgiev@kky.zcu.cz).
  
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===Experimental Design===
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==[[Projects/Synthetic Biology|Synthetic Biology]]==
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[[File:wiki_ExperimentalDesign.png|thumb|right|alt=model discrimination figure.|The model discrimination approach.]]
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[[File:New_lab.jpg|thumb|right|alt=-|Synthetic Biology wet lab.]]
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Systems biologists are often faced with competing models for a given experimental system.
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Synthetic Biology is often misinterpreted to be a discipline encompassing the available biological (cloning, cultivation, analysis, etc.) protocols as well as the established application areas (bioproduction, adaptive therapy, etc.).  While the laboratory limitations and application needs are important inputs and outputs to this area, we believe the primary and direct contribution of Synthetic biology is a systematic engineering method for developing biotechnology.  Our research focuses on practical design rules and efficient tuning algorithms with the purpose of making the synthesis of regulatory and signalling devices faster and more reliable.
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Performing experiments can be time-consuming and expensive. Therefore, a method for designing experiments that, with high probability, discriminate between competing models is desired. Model discrimination of biochemical models unfortunately poses a computationally difficult problem.  CeCyL is interested in solving this problem for special cases that are important in experimental design.  The solutions yield informative experimental inputs.  The solutions also guide the biological design to ensure that it can later be reliably modeled and predicted.
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===Gene Tuning===
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==Bioinformatics==
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[[File:wiki_GeneTuning.png|thumb|right|alt=gfp under control of placI.|GFP under control of pLacI.]]
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[[File:HLACompatibility.png|thumb|right|alt=HLA compatibility figure.|HLA compatibility.]]
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Transcription networks are commonly used in synthetic biology to implement a wide variety of regulatory, logic, and temporal functions.  Tuning of transcription networks is commonly achieved by design of the gene promoter regions. Characterized promoter libraries serve well in this design as an initial starting point (Hammer 2006). As with any engineered system, however, precise behavior is attained by in vivo fine tuning.  Model based tuning is made difficult by inherent biological model overparametrization (Gutenkunst 2008). Tuning using high throughput assays is also prohibitive both in terms of experimental workload and precision. CeCyL is working on developing precise model-free tuning protocols. These are protocols that are able to identify small differences between competing promoter designs and isolate the ones that yield desirable behaviors, e.g., robustness to common perturbations, fast activation times, sufficient temporal spacings, and correct equilibrium concentrations.
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Compatibility of the host and donor human leukocyte antigen systems is critical to the success of a transplant. Discrepancies in HLA loci produce host immune responses that lead to graft rejection. Full donor DNA sequencing, however, is too costly and hence partial typization of important loci is carried out. Georgiev Lab in collaboration with the University Hospital in Pilsen is interested in developing computational tools for the estimation of the missing DNA data.
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* [http://ccy.zcu.cz/registr/CNRDDstatistika.html MADORA] - Marrow Donor Register Analytics (MADORA) for the Czech National Register of Marrow Donors (CNRDD)
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* [http://ccy.zcu.cz/registr/CZ-HANA.html HANA] - Haplotype analyzer (HANA) for the Czech population.
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===Division Control===
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==[[Projects/Microfluidics|Lab-on-chip systems]]==
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[[File:wiki_DivisionControl.png|thumb|right|alt=gfp under control of placI.|Accurate protein partitioning through spatial-temporal mechanisms.]]
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[[File:master.jpg|thumb|right|alt=Silicon master for the PDMS soft-lithography.|A soft-lithography silicon master used for fabrication of the microfluidic devices at the Georgiev Lab.]]
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Individual cells are constantly subject to perturbations: exogenous perturbations such as temperature fluctuations, brownian motion related perturbations, and perturbations caused by cell division.  Cell division related perturbations are primarily caused by random partitioning of molecules between daughter cells and can be difficult to attenuate.  Important molecules, e.g., chromosomes, implement complex mechanisms to ensure equal partitioning.  Other molecules, e.g., the majority of proteins, are simply partitioned at random.  CeCyL is interested in developing simple mechanisms to regulate general protein partitioning.
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Time lapse of E. coli with an integrated Min D::GFP fusion protein. Observed spatial-temporal oscillations are critical for correct cell division.
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Lab-on-chip systems integrate one or more lab functions on a chip of just couple centimeters squared. Such systems are able to work with extremely low volumes of liquid samples, can significantly decrease costs of individual operations and decrease requirements on additional hardware. Hence they enable for instance implementation of affordable diagnostic tools for cancer or development of tools enabling selection of optimal therapy increasing treatment efficiency and its personalization for individual patients.
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Our research focuses on applications of the electric field in lab-on-chip systems in the form of dielectrophoretic effect based on polarization effect in the electric field. Dielectrophoretic effect may be used for measurement of cell properties on population level, their selective contactless manipulation or immobilization. At the same time, it may be combined with other electric field-based methods such as the electro-rotation, the impedance spectroscopy and the electro-poration, and with other technologies such as microscopy and optical data analysis.
  
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<mediaplayer width='550' height='300'>http://www.ccy.zcu.cz/movies/Osc_video.mov</mediaplayer>
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===Cell Sorting===
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[[File:wiki_CellSorting.png|thumb|right|alt=gfp under control of placI.|Characterization of DEP forces on different phenotypes.]]
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Numerous methods of cell separation exist.  Primitive methods  ignore cellular composition (size based separation).  Expensive methods utilize fluorescent markers together with expensive laser sorters (FACS).  Other methods require exogenous labels and known protein interactions (magneto-phoresis).  Such interactions can be non-specific.  Hence, only sufficiently disparate phenotypes can be isolated.  Dielectrophoretic separation is based on forces generated directly by the cellular  makeup.  Hence multiplexed separation and multilevel separation is possible.  Programmed cells can also be used as probes for logic enabled labeling.  CeCyL in collaboration with FEL UWB is interested in developing dielectrophoretic separation methods together with compatible biological devices.
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Dielectrophoretic cell focusing microfluidic device developed at CeCyL.  The presence of an electric field tuned to a specific frequency allows the cells to be focused by negative dielectric forces to the center of the channel.
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<mediaplayer  width='550' height='300'>http://www.ccy.zcu.cz/movies/DEP_Focusing.mp4</mediaplayer>
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Latest revision as of 09:09, 12 May 2017

The development of biological devices that transform living cells into biosensors, nano-factories, and therapeutic agents is the objective of synthetic biology. Georgiev Lab is a university wide research laboratory interested in innovations that make such devices reliable and efficient enough to make the biological systems a generally useful technology. We apply tools from engineering and synthetic biology to 1) build electromechanical devices co-designed with biological devices, 2) derive estimation and modeling methods specifically for biological systems, and 3) develop biological control mechanisms and theory.

If you are interested in joining us in this effort or if you are just simply interested, contact Dr. Daniel Georgiev (georgiev@kky.zcu.cz).

Synthetic Biology

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Synthetic Biology wet lab.

Synthetic Biology is often misinterpreted to be a discipline encompassing the available biological (cloning, cultivation, analysis, etc.) protocols as well as the established application areas (bioproduction, adaptive therapy, etc.). While the laboratory limitations and application needs are important inputs and outputs to this area, we believe the primary and direct contribution of Synthetic biology is a systematic engineering method for developing biotechnology. Our research focuses on practical design rules and efficient tuning algorithms with the purpose of making the synthesis of regulatory and signalling devices faster and more reliable.

Bioinformatics

HLA compatibility figure.
HLA compatibility.

Compatibility of the host and donor human leukocyte antigen systems is critical to the success of a transplant. Discrepancies in HLA loci produce host immune responses that lead to graft rejection. Full donor DNA sequencing, however, is too costly and hence partial typization of important loci is carried out. Georgiev Lab in collaboration with the University Hospital in Pilsen is interested in developing computational tools for the estimation of the missing DNA data.

  • MADORA - Marrow Donor Register Analytics (MADORA) for the Czech National Register of Marrow Donors (CNRDD)
  • HANA - Haplotype analyzer (HANA) for the Czech population.


Lab-on-chip systems

Silicon master for the PDMS soft-lithography.
A soft-lithography silicon master used for fabrication of the microfluidic devices at the Georgiev Lab.

Lab-on-chip systems integrate one or more lab functions on a chip of just couple centimeters squared. Such systems are able to work with extremely low volumes of liquid samples, can significantly decrease costs of individual operations and decrease requirements on additional hardware. Hence they enable for instance implementation of affordable diagnostic tools for cancer or development of tools enabling selection of optimal therapy increasing treatment efficiency and its personalization for individual patients. Our research focuses on applications of the electric field in lab-on-chip systems in the form of dielectrophoretic effect based on polarization effect in the electric field. Dielectrophoretic effect may be used for measurement of cell properties on population level, their selective contactless manipulation or immobilization. At the same time, it may be combined with other electric field-based methods such as the electro-rotation, the impedance spectroscopy and the electro-poration, and with other technologies such as microscopy and optical data analysis.


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