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Recent News

Upcoming Events

Dec
7
Mon
Biophysics Seminar: Ned Wingreen, PhD
Dec 7 @ 12:00 pm – 1:00 pm

National CancerInstitut/Center for Cancer Research

Dec
9
Wed
RCR Training – Bin Wu
Dec 9 @ 9:30 am – 10:30 am

“Make experiment reproducible again: RCR training for data integrity and reproducibility”

Faculty, staff, postdoctoral fellows and graduate students paid by sponsored funding are required to complete RCR Training. This training is also a graduation requirement.

Attendance will be taken.

Register your attendance on the day of the event by using the link below:

https://oit.med.jhmi.edu/RCR_Attendance/

Please use the Zoom link below to access the seminar:

https://jhjhm.zoom.us/j/98068574200?pwd=SVZFY0pHN2ZjdnFucE54RXZSS1lmdz09

Meeting ID: 980 6857 4200

Passcode: (see e-mail)

B&BC Seminar: Valeria Vasquez, Ph.D.
Dec 9 @ 1:30 pm – 2:30 pm

Title: Dietary fatty acids fine-tune cells mechanical response  

Affiliation: The University of Tennessee

Join Zoom Meeting
https://jhjhm.zoom.us/j/97661362913?pwd=TkFTL3VxZVFyRmdHRzUwbDlGSndsdz09

Meeting ID: 976 6136 2913
Passcode: (see announcement email)

Thesis Seminar: Joyce Lee
Dec 9 @ 3:00 pm – 4:00 pm
Student Evening Series
Dec 9 @ 6:30 pm – 8:30 pm

Join Zoom Meeting

https://JHUBlueJays.zoom.us/j/96683357920?pwd=NUpkZkVWZlNPR3NuOVVydWJ4OUxKQT09

 

Meeting ID: 966 8335 7920

Passcode: (see e-mail announcement)

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Trevor Zandi- Townsend lab

Title: Non-hydrolytic and reversible off-loading mechanisms of a meropenem-inhibited L,D transpeptidase 

Nearly one quarter of the world’s population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), and approximately 1.5 million people die of TB each year. TB is thus the deadliest infectious disease in the world. The cell wall of most bacteria contains a peptidoglycan layer and inhibitors of peptidoglycan biosynthesis, such as members of the β-lactam class, have achieved significant clinical success as antibiotic drugs, however these drugs have historically had limited efficacy against mycobacterial species. This has been overturned by the phase II clinical success of the β-lactam drug, meropenem, in patients with drug resistant pulmonary TB. Unlike other β-lactams, meropenem inhibits a non-canonical peptidoglycan biosynthesis enzyme family, the L,D transpeptidases, which cross-link peptidoglycan using a catalytic cysteine rather than a catalytic serine. It is known that meropenem forms a covalent adduct with the catalytic cysteine of L,D transpeptidases, but a detailed chemical inhibitory mechanism, critical for rational design of next-generation antibiotics, is absent. We have characterized small molecule products of an L,D transpeptidase–meropenem covalent adduct, and discovered competing off-mechanisms: reversible re-formation of meropenem, non-hydrolytic degradation, and hydrolysis. 

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Morgan Beckett- Bailey lab

DNA methylation is an important epigenetic mechanism that allows for regulation of gene expression and maintenance of genome stability. UHRF1 (Ubiquitin Like with PHD and RING Finger Domain 1), a multidomain, epigenetic regulator, has been shown to play a critical role in bridging both DNA methylation and chromatin remodeling. It recognizes and binds hemi-methylated DNA (hm-DNA) as well as trimethylated histone H3K9 (H3K9me3). Subsequently, UHRF1 recruits DNMT1 (DNA methyltransferase 1) to ensure accurate propagation of methylation patterns throughout DNA replication. Recent findings have shown that various intramolecular interactions between UHRF1 domains allow for regulation of both hm-DNA and H3K9me3 recognition. In the absence of hm-DNA, UHRF1 was found to prefer a closed conformation resulting in the inability to recognize histone H3K9me3. Conversely in the presence of hm-DNA, the SRA domain binds hm-DNA driving UHRF1 to adopt a locked, open conformation in which subsequent recognition of H3K9me3 can occur. Nevertheless, the exact nature of these allosteric, intradomain interactions remains incompletely understood. It has also been found that UHRF1 plays a notable role in promoting proliferation and has been shown to be overexpressed in several cancers, highlighting UHRF1 as a potential drug target for therapeutic applications. 

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Hope to see you all there!

Best, 

Miranda Hurst & Amy Fernandez

mhurst6@jhu.edu & ajfernandez@jhmi.edu

Overview

The Department of Biophysics and Biophysical Chemistry provides training for oustanding students with interests in such quantitative areas as crystallography, enzymology, kinetics, protein design, and mathematical computer modeling.