Welcome to the Biomolecular Engineering laboratory at BME
Our strategic research concept is to create novel molecules through biomolecular engineering to develop biosensing technologies dedicated to health care management.
Ultimately, we aim to create innovative theranostic biomolecules and biodevices which can aid in the recognition and/or diagnosis of medical conditions and provide medicine/treatment to patients suffering from various diseases (metabolic disorders, mental disorders, cancer, etc.).
The targets for our biomolecular engineering are enzymes, antibodies, binding proteins, receptors/transporters, aptamers, and synthetic molecules. With the combination of a variety of electrochemical principles (amperometric, potentiometric, voltametric, and impedimetric) and advanced platforms, we are developing innovative biosensing technologies to drive the improvement of human health and quality of life.
Currently, the Sode lab is focusing on the development of:
1. Novel in situ, real-time, multi-parameter biosensing systems
2. Innovative POCT sensing systems for biomarker detection
3. Novel biosensing systems for mental health care, brain diseases, and for diabetes care and ultimately,
4. Autonomous biosensing actuators and biosensing therapeutic molecules realizing smart drug delivery systems.
What is "Biomolecular Engineering"?
Biomolecular engineering is the design and/or creation of new biomolecules and/or the mimicking of biomolecules based on their structural and functional information. Our strategic approaches toward biomolecular engineering are based on knowing the existing and/or future requirements for accurate and precise monitoring of biomarkers that are essential for medical and health care management. Engineering of biomolecules is realized by introducing strategically designed mutations, replacing or inserting novel structures, and utilizing fusion technologies as well as in silico predictions. The creation of novel biosensing principles is accomplished by designing novel biomolecules with expected features suitable for these new biosensing principles. The discovery, design, and creation of novel biomolecules is the most promising and attractive strategy to develop novel biosensors dedicated to the analytical demands from a variety of fields; medical, health, environment, process monitoring, etc. Our research targets of biomolecular engineering that are dedicated to the development of novel biosensing systems are enzymes, antibodies, receptors, binding proteins, aptamers, and synthetic molecules (polymers).
PI: Dr. Sode’s most notable research activities are biomolecular engineering research topics, represented by the development of engineered enzymes which can be used in self-monitoring glucose sensing systems for diabetes. Specifically, Dr. Sode has focused on a family of enzymes called glucose dehydrogenases (GDHs), which serve as a scaffold and a template enzyme molecule to construct an ideal enzyme for use in self-monitoring of blood glucose (SMBG) as well as in continuous glucose monitoring systems. (CGM). In particular, Dr. Sode has focused on engineering the following enzymes/proteins: glucose oxidase, glucose dehydrogenases, cholesterol oxidase, lactate oxidases, fructosyl amino acid/peptide oxidases, glucose binding proteins, and fructosyl amino acid kinase/binding proteins. These enzymes/proteins are engineered by introducing strategically designed amino acid substitutions and/or using chimeric enzyme/protein construction to improve their performance for a specific application. Structural elucidation of the biosensing molecules are carried out to obtain necessary information to exploit our biomolecular engineering approach. Our group has also expanded research activities to include the science and engineering of novel protein groups, natively unfolded proteins. Natively unfolded proteins, or disordered proteins, are a group of proteins that have little or no ordered structure under physiological conditions. In particular, our group has focused on α-synuclein, a protein attributed to cause Parkinson’s disease (PD). Studies on the mechanism of amyloid formation and the use of amyloid fibrils for bio-nanostructure scaffolds are also reported.
This sentence seems a little out of place when I read it. There was no mention of amyloids before so I don’t really have context for how that ties into this research. I think it either can be deleted, or another sentence could be added to supplement the information presented.
“FAD dependent glucose dehydrogenases – Discovery and engineering of representative glucose sensing enzymes-”, Junko Okuda-Shimazaki, Hiromi Yoshida, , Bioelectrochemistry, 2019, available online 20 Nov. 2019, 107414, Volume 132, April 2020, 107414
“Designer fungus FAD glucose dehydrogenase capable of direct electron transfer”, Kohei Ito, Junko Okuda-Shimazaki, Kazushige Mori, Katsuhiro Kojima, Wakako Tsugawa, Kazunori Ikebukuro, Chie E. Lin, Jeffrey LaBelle, Hiromi Yoshida, Koji SODE, Biosens. Bioelectron., Jan 1, 2019, 123, 114-123, doi: 10.1016/j.bios.2018.07.027, 2018 Jul 26, [Epub ahead of print].
“Strategic design and improvement of the internal electron transfer of heme b domain-fused glucose dehydrogenase for use in direct electron transfer-type glucose sensors”, Kohei Ito, Junko Okuda-Shimazaki, Katsuhiro Kojima, Kazushige Mori, Wakako Tsugawa, Ryutaro Asano, Kazunori Ikebukuro, Koji SODE, Biosensors and Bioelectronics, Volume 176, 15 March 2021, 112911, https://doi.org/10.1016/j.bios.2020.112911 Epub 2020 Dec 17.
“Rational design of direct electron transfer type l-lactate dehydrogenase for the development of multiplexed biosensor”, Kentaro Hiraka, Wakako Tsugawa, Ryutaro Asano, Murat A Yokus, Kazunori Ikebukuro, Michael A Daniele, Koji SODE, Biosensors and Bioelectronics, Volume 176, 15 March 2021, 112933, https://doi.org/10.1016/j.bios.2020.112933 Epub 2020 Dec 25.
“Construction and characterization of FAD glucose dehydrogenase complex harboring truncated electron transfer subunit”, Junko Okuda-Shimazaki, Noya Lowe, Nana Hirose, Katsuhiro Kojima, Kazushige Mori, Wakako Tsugawa, Koji SODE, Electrochimica acta, 2018 July 1; 277: 276-286. doi: 10.1016/j.electacta.2018.04.060
What is "Biosensors"?
Biosensors are defined as “analytical devices incorporating a biological material, a biologically derived material or a biomimic intimately associated with or integrated within a physicochemical transducer or transducing microsystem, which may be optical, electrochemical, thermometric, piezoelectric, magnetic or micromechanical” (Turner et al., 1987). The history of biosensors began with the invention of a glucose sensor by Professor Clark in 1956, which was constructed through the combination of a Clark type oxygen electrode and the legendary enzyme, glucose oxidase (GOx). The most characteristic and yet indispensable component in biosensors is the biologically derived or mimicked biosensing molecule i.e., enzymes, antibodies, aptamers, binding proteins, receptors, synthetic receptors, molecularly imprinted polymers, cells etc. Biosensors have been developed by applying existing biomolecules, newly discovered/created biomolecules or engineered existing biomolecules. Currently, the most advanced biosensors are the glucose sensors used for continuous glucose monitoring (CGM) systems. Our future goals are to construct biosensors which are operated continuously for real-time in vivo monitoring of target molecules and to combine these with sensor-augmented therapeutic devices to provide predicted target concentrations.
Our research group is engaged in proposing new biosensing principles and the development of novel biosensors with innovative biomolecules dedicated to medical and health care management (metabolic disorders, brain injury, mental disorders, and neural sciences).
Currently, we have been developing biosensors for glucose (both finger-stick type and continuous glucose monitoring), glycated proteins (glycated albumin and glycated hemoglobin), insulin, lactate, lipids (cholesterol, triglyceride), biomarkers for traumatic brain injury (UCLH-1, GFAP), and compounds relating to mental health and neural science (cortisol, phosphoethanol amine, D-Ser, L-Glu, dopamine).
Our research topics in biosensing technologies include the development of enzyme/microbial sensors for diagnostic use, as well as for environmental and food monitoring. Most of these sensor systems employ novel enzymes that were engineered or isolated in our laboratory. These include direct-electron-transfer (DEDT) enzyme sensing systems employing protein-engineered enzymes and novel biosensing systems employing artificial ligands, such as molecularly imprinted polymers (MIPs) and DNA aptamers. We are using various sensor platforms, including screen-printed electrodes, gold electrodes, interdigitated electrodes, and gold micro-electrodes to construct innovative and practical electrochemical biosensing systems. We have also reported on the construction of a novel biofuel cell system employing engineered enzymes. The developed miniaturized biofuel cell uses direct electron transfer type glucose dehydrogenase in the anodic catalyst and could be used in combination with microsystems. Our representative research topics on biosensing technology is the development of electrochemical enzyme glucose sensors based on DET-type enzymes combined with chemical modification, nano-technology approaches, and cutting-edge transducers, including the innovative idea of “BioCapacitor”, which realizes a stand-alone, self-powered, and autonomous wireless glucose sensing system.
“Continuous glucose monitoring systems - current status and future perspectives of the flagship technologies in biosensor research –”, Inyoung Lee, David Probst, David Klonoff, Koji SODE, Biosensos and Bioelectronics (in press)
“Development of an Interdigitated Electrode-Based Disposable Enzyme Sensor Strip for Glycated Albumin Measurement”, Mika Hatada, Noya Loew, Junko Okuda-Shimazaki, Mukund Khanwalker, Wakako Tsugawa, Ashok Mulchandani, Koji SODE, Molecules 2021, 26(3), 734; https://doi.org/10.3390/molecules26030734
“Development of glycated peptide enzyme sensor based flow injection analysis system for haemoglobin A1c monitoring using quasi-direct electron transfer type engineered fructosyl peptide oxidase”, Mika Hatada, Satomi Saito, Satoshi Yonehara, Wakako Tsugawa, Ryutaro Asano, Kazunori Ikebukuro, Koji SODE, Biosensors and Bioelectronics Volume 177, 1 April 2021, 112984 https://doi.org/10.1016/j.bios.2021.112984 Online ahead of print.
“Third generation impedimetric sensor employing direct electron transfer type glucose dehydrogenase”, Yuka Ito, Junko Okuda-Shimazaki, Wakako Tsugawa, Noya Loew, Isao Shitanda, Chi E. Lin, Jeffrey LaBelle, Koji SODE, Biosens. Bioelectron. Mar 15, 2019, 129, 189-197, doi: 10.1016/j.bios.2019.01.018, 2019, Jan 16. [Epub ahead of print].
“Development of a third-generation glucose sensor based on the open circuit potential for continuous glucose monitoring”, Inyhoung Lee, Noya Loew, Wakako Tsugawa, Karunori Ikebukuro, Koji SODE, Biosens. Bioelectron., Jan 15, 2019, 124/125, 216-223, doi: I: 10.1016/j.bios.2018.09.099, 2018 Oct 9 [Epub ahead of print].