EPFL BioEngineering Talks

Weekly BioEngineering Talks (Lunch Provided)

INVITED SPEAKER:

Architecture and Dynamics of Molecular Machines for Biosynthesis: From Polyketide Assembly to RNA Transcription
Prof. Jin Young Kang, Korea Advanced Institute of Science & Technology (KAIST)
Host: Aerin Yang

Abstract:
Cells rely on sophisticated molecular machines to build molecules ranging from specialized metabolites to biological macromolecules such as nucleic acids and proteins. Despite acting on chemically distinct substrates, these systems share the need to coordinate catalytic reactions within precisely organized and dynamic macromolecular assemblies. In this seminar, I will discuss how cryo-electron microscopy (cryo-EM) reveals both the molecular architectures and reaction dynamics of two such biosynthetic machines.

First, I will present cryo-EM structures of the polyketide synthase (PKS) module of ClbB, a hybrid nonribosomal peptide synthetase–polyketide synthase involved in the biosynthesis of colibactin, a gut microbiome-derived genotoxin linked to colorectal cancer. The reducing domains of the ClbB PKS module adopt a noncanonical architecture that differs markedly from those of previously characterized modular PKSs. Its enoylreductase forms a central dimeric scaffold, whereas the monomeric dehydratase is positioned at the periphery, producing an unexpected organization of the catalytic domains. Bioinformatic analyses further identified related domain organizations across diverse bacterial phyla, suggesting that ClbB represents a broader, previously unrecognized class of modular PKSs.

I will then introduce a time-resolved cryo-EM platform that we developed using an integrated parylene thin-film mixer and sprayer. This platform enables reaction initiation and vitrification on the millisecond timescale while substantially reducing sample consumption. We are applying it to investigate the nucleotide addition cycle of Escherichia coli RNA polymerase. By sampling the reaction over a 0–400 ms time window, we seek to determine how closely related transcription intermediates are populated and interconverted during a single round of nucleotide addition cycle. Our initial results reveal a few intermediate states that were not observed in conventionally prepared steady-state samples, while also highlighting the analytical challenges associated with resolving transient and structurally similar states.

Together, these studies illustrate how cryo-EM can reveal both unexpected architectures of biosynthetic assembly lines and short-lived molecular transitions underlying fundamental cellular reactions.

Bio:
Jin Young Kang is an Associate Professor in the Department of Chemistry at KAIST, where her laboratory studies the structure and dynamics of macromolecular machines involved in transcription regulation and natural product biosynthesis. She received her PhD from KAIST and trained at The Rockefeller University with Roderick MacKinnon and Seth Darst before starting her independent group in 2019. Her research combines cryo-electron microscopy, X-ray crystallography, biochemistry, mass spectrometry, and computational approaches to understand how dynamic molecular complexes carry out biological functions. Her work has provided mechanistic insights into bacterial transcriptional pausing and termination, and microbiome-derived colibactin biosynthesis. Her group is also developing time-resolved cryo-EM technologies to capture transient structural states and investigate molecular processes in real time.

STUDENT SPEAKER:

Towards riboswitch design by ultradeep sequence-function-mapping and deep learning 
Charlotte Desczyk, Jeschek Lab


------------------------------------------------------------------------------

BioEngineering Talks mandatory EDBB Seminar Attendance (1st-Year PhD Students)

•  Attendance sheet to print HERE 

• Register HERE
• Attendance sheet to print HERE