Dr. Dan Fabris
Harold S. Schwenk Sr. Distinguished Chair in Chemistry
Department of Chemistry, University of Connecticut
Host: Eric May

Hunting for new antivirals capable of disrupting the dynamic ensembles of regulatory RNAs

Summary: In many RNA viruses, genomic sequences corresponding to regulatory (i.e., non-coding) domains can fold alternative conformations responsible for different biological functions. Disrupting their interconversion would represent an excellent strategy for inhibiting such functions and interfering with the viral lifecycle. Owing to the intrinsic challenge of resolving the structural heterogeneity of these RNA dynamic ensembles, traditional drug-discovery approaches have thus far failed to provide effective leads. The talk will illustrate a suite of approaches based on native mass spectrometry (nMS) and Ion Mobility Spectrometry (IMS) MS, which afford the ability to distinguish the individual members of an RNA ensemble and to assess the effects of ligand binding on their mutual distribution. The talk will discuss the unique features that make nMS capable of taking accurate snapshots of all unbound/bound species present at equilibrium in solution when putative ligands are mixed with target RNAs. It will also show that combining nMS with IMS allows one to monitor RNA conformational landscapes before and after addition of ligand, which can reveal possible conformer selectivity. The information provided by these approaches will provide the foundations for developing conformer-specific antivirals with greatly reduced off-target toxicity.

Bio: Dan Fabris is a Professor and the Harold S. Schwenk Sr. Distinguished Chair in Chemistry. He received a Ph.D. at University of Padova (Italy) and trained as a post-doc at the National Research Council in Padova and the University of Maryland Baltimore County (UMBC). After raising to Professor at UMBC, he was recruited by University at Albany (SUNY) to become one of the founding members of The RNA Institute. He specializes on the development of novel approaches for the investigation of the structure/function relationships of RNA, which are based on mass spectrometric (MS) techniques. He pioneered native MS and crosslinking techniques for the structural elucidation of RNA and protein-RNA complexes that are not directly amenable to high-resolution techniques. At University of Connecticut since 2020, he is now exploring new strategies combining native MS with Ion Mobility Spectrometry (IMS) MS to investigate the effects RNA post-transcriptional modifications and ligand binding onto the structure and dynamics of regulatory RNAs.

Publication

Fabris Lab website

This week in Cell and Developmental Biology Journal Club, Anna Moriartywill lead a discussion of“Allelic transcriptomic profiling identifies the role of PRD-like homeobox genes in human embryonic- cleavage-stage arrest” by Gao et al., 2025.

https://mcb.media.uconn.edu/wp-content/uploads/sites/2341/2025/03/Guo-et-al-2025.pdf

Department of Molecular and Cell Biology

University of Connecticut

Announces the

Oral Dissertation Defense for the Doctoral Degree

Alexei Cooper

B.S. University of Vermont

Insights into gene exchange, cell morphology, and quorum sensing in the halophilic archaeon Haloferax volcanii

Thursday, March 6, 2025

2:00 PM

Webex
https://uconn-cmr.webex.com/uconn-cmr/j.php?MTID=m407089893fca159c06136ad1c211e541

Password: H.volcanii

Major Advisor: Dr. Thane Papke
Co-Advisor: Dr. Daniel Gage
Associate Advisor: Dr. Peter Gogarten
Associate Advisor: Dr. Aoife Heaslip
Associate Advisor: Dr. Simon White
Examiner: Dr. Geo Santiago-Martinez

Link to Dissertation

Heather Jamieson
Goldhamer Lab

Developmental Regulation of the Myogenic Determination Gene, MyoD

Tristan Evans
Robinson Lab

Interactions of the E.Coli 70S:BipA Complex

Lilian Kabeche
Assistant Professor, Molecular Biophysics and Biochemistry, Yale School of Medicine
Host: Barbara Mellone

Redefining the relationship between replication stress and centromere dysfunction

The link between replication stress and centromere dysfunction has been established, yet the molecular mechanism remains elusive. Our data demonstrates that replication stress reduces CENP-A occupancy at centromeres and is subsequently accumulated in nucleoli in an ATR-dependent manner; demonstrating a novel link between replication stress and centromere dysfunction.

About Dr. Kabeche:
Lily received her Ph.D. at Dartmouth College in Dr. Duane Compton’s laboratory focusing on how spindle microtubules are regulated to ensure proper attachment to chromosomes. She transitioned to Dr. Lee Zou’s lab at MGH/Harvard, where she focused on the role of a DNA damage response kinase, ATR, in mitosis. She elucidated that ATR was constitutively active in an DNA damage independent manner at the centromere, where it promoted faithful chromosome segregation by regulating spindle microtubules. As an Assistant Professor, Lily has focused on elucidating the non-canonical roles of DNA damage response kinases. Her lab has demonstrated new roles for ATR in centromere identity and laminar structure in interphase and defined new roles for other DNA damage response kinases, including Chk2 in mitosis.

https://pubmed.ncbi.nlm.nih.gov/37163376/
https://pubmed.ncbi.nlm.nih.gov/29170278/

Kabeche Lab

GO:MCB will be hosting our first coffee hour of the Spring semester next week! Join us on March 12 in BPB 201 from 9:00-11:00 AM to catch up with your fellow grad students, drink some coffee, and eat bagels. We look forward to seeing you all soon!

MCB Diversity, Equity, Inclusion meeting Wednesday, March 12, at 11am Webex room:https://uconn-cmr.webex.com/meet/smh15104

Anyone who would like to drop in is welcome to.

- Sarah Hird

Trauma Informed Pedagogy
Cutting through the fluff, embracing reas strategies

Speaker: Dr. Mays Imad, Associate Professor of Biology, Connecticut College

This week in Cell and Developmental Biology Journal Club, Ingrid Schwarzwill lead a discussion of “Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors” byMavrommatis et al., 2023.

Lee Dollar
Heaslip Lab

Investigating the role of an essential dynamin-like protein in Toxoplasma gondii.

Edward Russell
Hanlon Lab

Inserting a unique sequence and phenotypic marker on the B chromosome

MCB Faculty Meeting

Dr. Priya Vanaja, DVM, PhD
Associate Professor of Immunology
Director, Graduate Program in Immunology
UConn Health

Host: Ken Campellone

Bacterial toxin maneuvering of host cell death

The talk will focus on (i) how Shiga toxin, an exotoxin produced by enterohemorrhagic Escherichia coli, inhibits inflammasome responses in toxin-resistant innate immune cells, and (ii) the molecular mechanism by which Shiga toxin kills susceptible cells in the human body.

About Dr. Vanaja:

I have a long-standing interest in understanding the host-bacterial pathogen interaction mechanisms that govern human infectious diseases. I have more than fifteen years of experience in investigating both pathogen and host aspects of enterohemorrhagic Escherichia coli (EHEC) and Shiga toxin-mediated diseases. My laboratory at UCONN Health investigates the mechanisms of bacterial pathogen activation and evasion of innate immunity in the context of EHEC infection. Our studies revealed the essential role of bacterial outer membrane vesicles in cytosolic LPS delivery and noncanonical inflammasome activation, thus providing a mechanistic basis for cytosolic LPS entry during extracellular Gram-negative bacterial infection. We have also demonstrated a TLR4-independent role for CD14 in noncanonical inflammasome activation in vivo. A recent study from my laboratory unraveled a novel inflammasome suppressive function of the well-known bacterial virulence factor, Shiga toxin. Our studies have also identified a novel bacterial autotransporter-mediated mechanism that targets TFE3 transcription factor to block type I IFN responses.

A bacterial toxin co-opts caspase-3 to disable active gasdermin D and limit macrophage pyroptosis

Shiga toxin suppresses noncanonical inflammasome responses to cytosolic LPS

Vanaja website

This week in Cell and Developmental Biology Journal Club, Andrew Deierlein will lead a discussion of “Host-microbiome interactions in distinct subsets of preterm labor and birth” by Galaz et al., 2023.

Submissions are now being accepted for the 11th Annual Undergraduate Research Colloquium in Molecular and Cell Biology. Graduating senior MCB or Biophysics majors are encouraged to present their research project as a short 15 minute talk. Graduating Biology majors whose project is supervised by an MCB faculty member are also invited to present their work. There will be two sessions:

SESSION I:
Tuesday, April 15, 2025
3:30 - 4:30 PM | BPB 130

SESSION II:
Friday, April 18, 2025
12:30 - 1:30 PM | BPB 131

The top three MCB presentations will be selected for participation in the All-Biology Symposium (to be held on May 2) and will be eligible for multiple awards.

If you would like to participate, please e-mail the following information by Friday, March 28
to mcboffice@uconn.edu with
MCB Research Colloquium in the subject line.

Student Name:
Major:
Email:
Thesis/presentation Title:
Thesis Research Adviser:
Honors Adviser (if applicable):
Short bio and current research interests:
Availability: **Please provide time slots during which you have classes or labs that would conflict with your ability to participate. Even if you have no conflicts, please indicate this**

GO:MCB would like to treat you for lunch this Friday before our RIPS seminar! Please join us on March 28^th in the BPB Atrium from 11:45 - 12:20 PM for pizza and a chance to catch up with your fellow colleagues. We look forward to seeing you there!

Rosie Mirabella
Campellone Lab

Functions for the actin nucleation machinery in innate immune signaling

Maddy O’Connor
Mellone Lab

Determining the localization of centromere-derived transcripts in Drosophila melanogaster