Research
Research
Although this section covers a broad range of techniques and research topics, they are unified by a central question: How can we understand, identify, and predict synergism in complex chemical mixtures? Specifically, my work asks: (1) what synergism truly means in biological systems and how it can be distinguished from additivity; (2) whether mixture toxicity can be predicted, with or without synergistic interactions; and (3) what level of mechanistic understanding is necessary to make these predictions robust and extendable.
The species of interest are mostly insects, or more broadly terrestrial invertebrates, including both target and non-target species. During my Ph.D. and first postdoctoral position at Seoul National University, my work mainly focused on pesticide efficacy against pest species and integrated pest management strategies. In my second postdoctoral position at Lund University, my research has shifted more toward non-target species and environmental risk assessment, particularly non-bee pollinators such as Eristalis tenax and Pieris napi. Across these systems, my broader goal is to balance the two key axes of pesticide application—efficacy and safety—by developing approaches and insights into how chemical mixtures act in biological systems.
Modeling and Optimization of Synergistic Interactions
Understanding the bioactivities of mixtures, including botanical extracts, formulations, and tank mixtures, is challenging due to the complex interactions among components. I evaluate conventional reference (null) models, such as Loewe additivity, Bliss independence, HSA, and their extensions, to determine their applicability in predicting the mixture toxicity of insecticides and botanicals. Recognizing their limitations in capturing intermolecular interactions, I also explore parametric synergy models like BRAID, MuSyC, and Zimmer models, which provide greater precision in quantifying dose-dependent interactions but require extensive experimental data and often yield conflicting parameter estimates. To improve predictive accuracy, I apply mixture experimental design, developing mathematical models that capture nonlinear interactions in mixtures of botanicals. Additionally, I use single- and multi-objective optimization algorithms to fine-tune the blending ratios, ensuring the balance among efficacy, ecotoxicity, and phytotoxicity. These data-driven approaches provide a reliable framework for designing highly effective, selective, and sustainable mixtures of insecticides and botanicals for pest management.
Figs. Objective space of Pareto sets when blending individual compounds (top) versus blending extracts directly (bottom) (Yoon and Tak 2024, Journal of Agricultural and Food Chemistry).
Methodology for identifying synergism
For my Master's thesis, I developed synpdx, an R package designed to identify drug synergism in Patient-Derived Xenograft (PDX) studies. The framework addresses the challenges of correlated data and irregular longitudinal sampling by adaptively fitting a library of tumor growth and drug effect models. It then utilizes the optimal model to perform hypothesis testing via distance-based statistics. Currently, I am adapting this framework to identify synergism based on insect population growth dynamics.
Fig. (a) Experimental design of PDX studies. (b–c) Adaptive model fitting and selection.
(d–e) Hypothesis testing.
Mechanism of synergistic interactions
I investigate synergistic interactions that enhance insecticidal activities beyond the additive effects. My research focuses on metabolic synergy, where one compound inhibits the detoxification enzymes of another; target-site synergy, where one compound allosterically modulates the physiological target of another to amplify toxicity; and physicochemical synergy, where one compound enhances the cuticular penetration of another. Understanding these mechanisms is key to optimizing insecticidal formulations and improving pest control efficacy.
Fig. Electrophysiological response of larval motor nerve trunk from CNS. β-Myrcene alone was not able to exert any neurophysiological effect.
(Yoon and Tak 2023, Journal of Pest Science)
Figs. Collection, extraction, and concentration of spent hop from wastes of local beer brewery in Seoul (Yoon and Tak 2023, Journal of Pest Science)
Natural products as novel synergists
I have experience in collecting, extracting, and analyzing plant-derived bioactive compounds for their potential use in pest management. I utilize various extraction techniques, such as hydrodistillation, solvent extraction, and solid-phase microextraction. Also, GC-MS/MS and HPLC are used to quantify key components that may contribute to biological activities.
I have explored the potential of agricultural industry by-products as pesticide (or synergist) cancidates. As a big fan of craft beers and a home brewer by myself, I collaborated with local breweries. I investigated a beer brewing by-product and identified β-myrcene in volatile fractions of spent hop can act as insecticide synergist and repellent against Spodoptera frugiperda.
Computer vision for studying insect behaviors
Behavioral studies often provide crucial evidences in chemical ecology and toxicology. However, conventional physical marking methods (stickers, paints, dyes) can alter insect behavior, unsuitable for small species, and limited to basic metrics like distance moved, velocity, and time spent in specific areas.
To overcome these limitations, I employ computer vision techniques, including convolutional neural networks and contour detection, to automate behavioral analysis in a non-invasive, detailed, and quantifiable manner. This approach enables measurement of subtle behaviors such as antennal movement, leg angles, and body tilting, which were previously challenging to analyze. Additionally, many toxicological symptoms, such as convulsions, tremors, and prostration, lack standardized quantification. By applying computer vision, I redefine these terms into measurable metrics, transforming them into robust toxicological evidence. Furthermore, I integrate classification and clustering algorithms to analyze insect responses to novel compounds. This approach enables me to predict modes of action (article submitted), synergistic mechanisms between insecticides (article in preparation), insecticide resistance mechanism, repellency, attraction, and host selection.
Figs. Automated bodypart detection of imidacloprid-treated Aphis gossypii Glover (top) and prallethrin-treated Musca domestica L. (bottom)
Testing guidelines for biocides and repellents
Working across these areas has led me to develop an interest in the regulatory aspects of pest management. I have contributed to governmental testing guidelines for biocidal products and participated in developing a consumer information website on pest control products. My works include:
1) Participating in the formulation of official protocols for evaluating insecticidal and repellent products. To improve affordability and reproducibility, I designed testing materials to be 3D-printable, ensuring accessibility across different laboratories.
2) Helping develop a consumer information website, which includes safety guidelines and a whistleblowing system for reporting product issues.
3) Assessing the legal status of synergists and natural products, contributing to discussions on their regulation and approval.
Figs. Diagrams of assay devices employed for choice repellency test under closed and opened condition are shown in (A) and (B) respectively. Diagram of units for no-choice test under closed environment is shown in (C) (Yoon and Tak 2022 & 2024, Journal of Asia-Pacific Entomology).
Electrophysiology
I have experience in in vivo and in vitro electrophysiology, recording neural activity to study how insecticides and plant-derived compounds affect insect nervous systems. My skill set includes:
1) TTM and DLM recordings in the Giant Fiber System in Diptera
2) Extracellular recordings of central motor nerves in Diptera & Lepidoptera
3) Intracellular recordings of neuromuscular junctions in Diptera & Lepidoptera
4) Electroantennogram (EAG) in Diptera, Blattodea, Lepidoptera, & Hymenoptera
5) Electropenetrogram (EPG) in Aphids
Figs. Recording stations for Giant Fiber System, central motor nerves,
and neuromuscular junction recordings (top), and EAG recordings (bottom).