Caltech Postdoc Launch Seminar

Lunch will be served at 11:45 AM

Dr. Jacob M. Kirsh

Cryo-EM Structures of Human Phosphoglycosyltransferase DPAGT1 Elucidates Key Interactions for Catalysis and Inhibition

Protein glycosylation is an essential posttranslational modification influencing protein function and cell-cell signaling. The 92 kDa homodimeric membrane enzyme DPAGT1 plays a critical role in the human N-linked glycosylation pathway by catalyzing its first, committed step, and misregulation and mutation of DPAGT1 are directly linked with myriad cancers and congenital disorders. Despite its importance, only a few crystal structures of DPAGT1 have been solved, leaving open a number of questions about its catalytic mechanism. Moreover, there are no approved treatments for DPAGT1-related diseases, possibly due to a dearth of inhibitor-bound structures. Here, we present a cryo-EM structure of DPAGT1 bound with a novel anticancer inhibitor, the first cryo-EM structure of DPAGT1 to our knowledge. The structure clarifies lingering questions from the crystal structures, such as the binding position of a catalytically relevant lipid POPG molecule. It also provides information on chemical interactions at the dimer interface that were not previously resolved. Comparison to the bacterial homolog, MraY, allows critical analysis for understanding how new antibiotics can be engineered that are not cytotoxic to human cells.

Dr. Kenny Lau

Probing Inflation Physics at South Pole

The ΛCDM model successfully describes the large-scale evolution of the Universe from a hot, dense and nearly homogeneous initial state. Cosmic inflation extends this framework by introducing a brief period of exponential expansion, which naturally sets these initial conditions. A key prediction of inflation is a background of primordial gravitational waves, which would leave a distinctive imprint of B-mode polarization in the Cosmic Microwave Background (CMB), a signal yet to be observed.

The BICEP/Keck collaboration has operated a series of CMB polarimeters at the South Pole for over a decade, targeting degree-scale B-modes across ≈ 2% of the sky. In this talk, I will present maps from data through the 2024 season. The latest scientific results constrain the tensor-to-scalar ratio to σ(r) = 0.009, the strongest limit to date. Several previously popular inflationary models are now strongly disfavored. Forecasts suggest that combining upcoming BICEP/Keck and SPT data could tighten this constraint to σ(r) ≈ 0.001.

For more information, please contact Sejun Kim by email at [email protected] or visit this link to fill up the form and nominate yourself as a speaker.