Lim, Chunghun (임정훈)

Department

Department of Biological Sciences(생명과학과)

Website

https://sites.google.com/view/thelimlab/

Lab

Neurogenetics & Ribonomics Lab. (Neurogenetics & Ribonomics 연구실)

Research Keywords

분자신경생물, 단백질 번역, 퇴행성 뇌질환, 행동신경유전, Molecular Neurobiology, Ribosome Biology, Translation, Neurodegeneration, Behavioral Genetics

Research Interests

# Current Research
1. Decoding Non-canonical TranslationGene expression is central to all facets of physiology and its mechanistic basis had long been studied in the context of classical paradigm of transcription and translation. However, recent advances in RNA biology have revealed the robustness of “non-canonical” translation of which initiation occurs at non-AUG codons that associate with repetitive sequences, or at near-cognate start codons (i.e., AUG-like codon sequences), challenging a very fundamental principle of translation initiation. What remain to be addressed would be: 1) how translation factors and ribosomal machinery could “read” the code on mRNA molecules to initiate different types of non-canonical translation, and 2) why animals have evolved these unusual translation mechanisms on top of the canonical one. We employ molecular, genetic, genomics, and biochemical strategies (e.g., CRISPR/Cas9, RNA-seq, and mass-spec) to answer these fundamental questions and discover novel molecular principles underlying non-canonical translation in human cell cultures. Given that non-canonical translation has been shown to contribute to the expression of viral proteins or pathogenic cellular proteins relevant to neurological disorders, our findings should have clear, clinical implication in the development of new anti-viral drugs and better treatment of neurodegeneration.
2. Molecular Mechanisms Underlying Neurodegenerative DiseasesEmerging evidence indicates that post-transcriptional gene expression (i.e., molecular mechanisms that regulate gene expression after mRNAs are transcribed from DNA template) plays crucial roles in supporting neural development, function, and physiology. Consistently, genetic mutations in RNA-binding proteins and regulatory RNAs have been shown to closely associate with neurological disorders in human. We previously demonstrated that an RNA-binding protein ATAXIN-2 forms two functionally distinct protein complexes with its associating factors LSM12 and ME31B/DDX6, respectively, to sustain circadian locomotor behaviors (e.g., daily sleep-wake cycles). We now expand our working model to degeneration in iPSC(induced pluripotent stem cells)-derived motor neurons from ALS patients (amyotrophic lateral sclerosis; also known as Lou Gehrig’s disease) and transgenic Drosophila neurons to elucidate how genetic mutations in RNA-binding proteins and regulatory RNAs cause neurodegenerative diseases such as ALS and frontotemporal dementia (FTD). Our studies will help develop novel therapeutic strategy to efficiently treat those RNA-relevant neurological disorders.
3. Neural and Genetic Bases of Sleep Behaviors and Sleep-relevant PhysiologySleep is essential physiology that is well-conserved among animal species. However, molecular and neural mechanisms underlying sleep behaviors still remain elusive. We exploit Drosophila as our model system to understand 1) how our genes and neurons are functionally organized into sleep-regulatory pathways to support sleep homeostasis; 2) how the sleep-regulatory pathways intimately interact with the environment to adaptively adjust sleep behaviors, thereby manifesting sleep plasticity; and 3) how a lack of sleep could dominantly affect higher-order brain function and metabolism. Our studies will provide the neuro-genetic landscape of sleep regulation in Drosophila, hinting the fundamental principles of how human brain reciprocally controls sleep along with other sleep-relevant physiology.