Jung Lab - Research

Research

Biological systems are highly complicated but at the same time remarkably precise and dynamic. These systems are built through well-organized self- (or assisted-) assembly processes of various biomolecules such as DNA/RNA, proteins, and lipids. These specific collections of multiple biomolecules (let’s call them biomolecular assemblages) can show distinct and often more potent activities than separated individual biomolecules.

The goals of our research group are to elucidate working principles of nature’s dynamic bio-assemblies (or assemblages) and to use these principles in various biochemical applications. Our primary strategic approach is to engineer artificial biomolecular (mostly protein) assemblies, with which many facets of bio-assemblages can be investigated.

Frequently used research techniques in our Lab are nucleic acids/protein engineering; high-order biomolecule assembling; biomolecular interaction analysis; structural analysis, cellular imaging, etc ...

Currently, our research group has three major research topics (three sub-groups).

1. Artificial protein assemblies and bioanalysis (biosensors)

Supramolecular protein assemblies (also called protein nanostructures) provide novel nano-architectures with molecular precision and unlimited functionalities. These well-defined artificial protein assemblies will be highly effective to understand and also manipulate biomolecular assemblages. Ideally, we would like to direct spatial organization of functional proteins with tailored structures and sizes. And, ultimately, we want to create artificial protein machines. A below figure shows several examples of artificial protein assemblies that were fabricated in our group.

Protein multivalency, particularly multivalent protein interactions, is a key principle in many biological processes. However, little is known about the principles of multivalent protein interactions, which can achieve highly enhanced but also dynamic binding between various biological systems. High-order protein scaffolds, such as those fabricated in our lab, will be highly beneficial tools not only to study but also to use and control protein multivalency. One of our primary goals (with an ultimate ambition to understand bio-assemblies) is to elucidate the working mechanisms of biomolecular multivalent interactions (or multivalency) and also to apply these mechanisms to develop highly effective biosensors.

2. Chemistry of biomolecular liquid-liquid phase separation (LLPS)

Eukaryotic cells utilize various interior compartments to control highly complex biomolecular reactions in space and time. In addition to conventional membrane-bound organelles, many membrane-less compartments, which are condensed with distinct sets of biomolecules without discrete lipid bilayer barriers (therefore also termed biomolecular condensates), have been reported. A growing body of studies indicate that multivalent interactions between scaffold proteins drive liquid-liquid phase separation (LLPS) of biomolecular solutions, leading to liquid-like condensate droplet formation.

We want to find out working chemical principles of these biomolecular LLPS and to even manipulate these processes to create artificial bio-droplets (bio-assemblages) with unprecedented properties. By precisely managing protein assembly (or multivalent interactions), we have been developing simplified and therefore controllable protein LLPS model systems. With these models, we are trying to reveal formation and also behaving chemistry of biomolecular LLPS. In addition, we are highly interested in accurately analyzing bio-reactions inside bio-droplets.

3. Artificial biomolecular assemblages for bio-medicine (drugs & vaccines)

We believe that well-coordinated bio-assemblages can be powerful medical delivery vehicles for biomolecules such as biopharmaceuticals or vaccines. Our goal is to make artificial/synthetic biomolecular assemblages with modularity, where we can selectively put together targeted drugs or vaccines, ideally with intended densities, sizes, and also targeting abilities. Our knowledge on protein assembly and phase separation processes will be utilized to synthesize these assemblages. Previously, we developed protein cages that can selectively uptake chemical drugs and release to target cells.