Karen Sarkisyan
Group Members
Funding
“We create molecular technologies to study life and to engineer organisms with new behaviours”
We work in several research directions, both basic and applied, from studying structure-function relationship in proteins to engineering bacterial strains that can perform directed evolution without human involvement. We combine our interest in new technologies, high-throughput assays and automation to engineer organisms.
Previously, we have worked on fluorescent protein development, high-through put assays for measuring protein activities, mechanisms of bioluminescence and development of transgenic bacteria and plants.
At the MRC LMS we are approaching these and other problems from the perspective of synthetic biology, investing time into automation of our molecular biology routines and creating new molecular technologies for light-based computation and communication of cells. Additionally, we will work on studying structure-function relationship in proteins with the aim to compare properties of various regions of the protein sequence space in a systematic manner.
For more information visit the lab website: https://designing.bio.
Supplementary video 1 from Sarkisyan KS*, Bolotin DA*, Meer MV, et al. (2016). Local fitness landscape of the green fluorescent protein. Nature 533, 397–401. doi:10.1038/nature17995. This is the 3D-rendering of our dataset that is also depicted in Figure 1b in the article. The protein sequence is arranged in a circle, with the N terminal and the chromophore labelled on the outer circle. Black line markers outside the fitness landscape representation are positioned every 10 sites of avGFP. The Z-axis, height, represents the level of fluorescence, which is colour-coded from green to black. The surface is shown as the median fluorescence brightness levels of all mutations at a given site with fluorescence levels conferred by individual mutations shown by dots. The centre represents the fluorescence of avGFP with distance away from it corresponding to the number of mutations in the genotype. The median surface extends up to genotypes with 10 mutations.
Selected Publications
Mitiouchkina T , Mishin AS , Somermeyer LG , Markina NM, Chepurnyh TV, Guglya EB, Karataeva TA, Palkina KA, Shakhova ES, Fakhranurova LI, Chekova SV, Tsarkova AS, Golubev YV, Negrebetsky VV, Dolgushin SA, Shalaev PV, Melnik OA, Shipunova VO, Deyev SM, Bubyrev AI, Pushin AS, Choob VV, Dolgov SV, Kondrashov FA, Yampolsky IV, Sarkisyan KS. (2020) Plants with genetically encoded autoluminescence. Nature Biotechnology. https://doi.org/10.1038/s41587-020-0500-9
Ding SS, Romenskyy M, Sarkisyan KS, Brown AEX. (2020). Measuring Caenorhabditis elegans Spatial Foraging and Food Intake Using Bioluminescent Bacteria. Genetics. 214 (3), 577-587.
Pokusaeva VO , Usmanova DR , Putintseva EV , Espinar Calvo LM, Sarkisyan KS, Mishin AS, Bogatyreva NS, Ivankov DN, Akopyan AV, Avvakumov SY, Povolotskaya IS, Filion GJ, Carey LB, Kondrashov FA. (2019). An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1008079
Fleiss A and Sarkisyan KS. (2019). A brief review of bioluminescent systems. Current Genetics. 65, 877-882.
Kotlobay AA*, Sarkisyan KS*, Mokrushina YA*, Marcet-Houbene M*, Serebrovskaya EO*, Markina NM, Somermeyer LG, Gorokhovatsky AY, Vvedensky A, Purtov KV, Petushkov VN, Rodionova NS, Chepurnyh TV, Fakhranurova LI, Guglya EB, Ziganshina R, Tsarkova AS, Kaskova ZM, Shender V, Abakumov M, Abakumova TO, Povolotskaya IS, Eroshkin FM, Zaraisky AG, Mishin AS, Dolgov SV, Mitiouchkina TY, Kopantzev EP, Waldenmaier HE, Oliveira AG, Oba Y, Barsova E, Bogdanova EA, Gabaldón T, Stevani CV, Lukyanov S, Smirnov IV, Gitelson JI, Kondrashov FA, Yampolsky IV. (2018). A genetically encodable bioluminescent system from fungi. PNAS. 115 (50) 12728-12732.
* these authors contributed equally
We identified key components of the fungal bioluminescent system and studied its evolutionary history. This is the first fully genetically encodable eukaryotic bioluminescent system which means that we can now create not only glowing microbes but also glowing animals and plants.
Sarkisyan KS*, Bolotin DA*, Meer MV, Usmanova DR, Mishin AS, Sharonov GV, Ivankov DN, Bozhanova NG, Baranov MS, Soylemez O, Bogatyreva NS, Vlasov PK, Egorov ES, Logacheva MD, Kondrashov AS, Chudakov DM, Putintseva EV, Mamedov IZ, Tawfik DS, Lukyanov KA, Kondrashov FA. (2016). Local fitness landscape of the green fluorescent protein. Nature 533, 397–401, doi:10.1038/nature17995.
* these authors contributed equally
We characterized about 50,000 mutants of a protein-coding gene depicting for the first time the fitness landscape for an entire protein and revealing that the major structural factor behind the epistatic interactions is the contribution of mutations to the protein folding energy. We also presented evidences that molecular rules acting on protein evolution at local and global scales are likely similar.
Sarkisyan KS, Goryashchenko AS, Lidsky PV, Gorbachev DA, Bozhanova NG, Gorokhovatsky AY, Pereverzeva AR, Ryumina AP, Zherdeva VV, Savitsky AP, Solntsev KM, Bommarius AS, Sharonov GV, Lindquist JR, Drobizhev M, Hughes TE, Rebane A, Lukyanov KA, Mishin AS. (2015). Green fluorescent protein with anionic tryptophan-based chromophore and long fluorescence lifetime. Biophysical Journal 109:380-389, doi:10.1016/j.bpj.2015.06.018.
We created the first fluorescent protein with stable tryptophan-based chromophore in anionic state. This protein has the longest fluorescence lifetime among all known fluorescent proteins.
Sarkisyan KS*, Zlobovskaya OA*, Gorbachev DA*, Bozhanova NG, Sharonov GV, Staroverov DB, Egorov ES, Ryabova AV, Solntsev KM, Mishin AS, Lukyanov KA. (2015). KillerOrange, a Genetically Encoded Photosensitizer Activated by Blue and Green Light. PLOS One 10:e0145287; doi: 10.1371/journal.pone.0145287.
* these authors contributed equally
We created the first genetically encoded photosensitizer with orange emission. It can be used simultaneously with other photosensitizers for independent optogenetic control of cell populations.
Sarkisyan KS, Yampolsky IV, Solntsev KM, Lukyanov SA, Lukyanov KA, Mishin AS. (2012). Tryptophan-based chromophore in fluorescent proteins can be anionic. Scientific Reports 2:608, doi:10.1038/srep00608.
We engineered the first fluorescent protein with the tryptophan-based chromophore in anionic state. This was also the first evidence that tryptophan residue can exist in anionic state in biological systems.
