Title: I. Process Chemistry at AbbVie II. My Perspective of Some Similarities and Differences in Academia and Industry; Host: Jianing Li

Host: Rory Waterman

Host: Severin T. Schneebeli

Host: Christopher Landry

Title: Fine-tuning calcium responses in cells generated through neurotransmitters

Abstract:
There are many ways that cells receive and interpret information, and one of the most important is the G protein pathway, specifically GPCR-Gαq-phospholipase Cβ. This pathway relays information from hormones and neurotransmitters outside the cell to elicit calcium signals inside the cell. These calcium signals in turn cause cell-specific responses such as movement, division or protein synthesis. While the major aspects of this signaling system are known, cells have devised methods to amplify or attenuate calcium signals depending on the environmental conditions and type of cell. This seminar will discuss some of these mechanisms.

Host: Jianing Li

Title: Epigenetic-based Therapeutics to Improve Learning and Memory

Host: Matthias Brewer

Topic: Multiscale Modeling for Chemistry and Biochemistry

Speakers:

Professor Charles L. Brooks III, University of Michigan

Title: Exploring Free Energy Landscapes in pH, Chemical and Sequence Spaces

Professor Teresa Head-Gordon, University of California Berkeley

Title: Coarse Graining Electrons: Fast and Accurate Representations of Electrostatic Interactions

Professor Ken A. Dill, Stony Brook University, Laufer Center for Physical and Quantitative Biology

Title: Challenges in Reaching Bigger, Better, Faster in Physical Simulations of Proteins

Organizers:

Jinaing Li and Jose Madalengoitia

Title: Applied biophysics to control stability and molecular interactions of therapeutic antibodies for candidate selection and formulation design

Abstract: Therapeutic proteins are among the fastest growing segments of the pharmaceutical industry, and represent most of the current blockbuster medicines on the market. Proteins are commonly manufactured and delivered in liquid solution, and the molecular-scale interactions between proteins and their environment (and each other) dictate key biophysical properties such as solution viscosity, solubility, and multi-scale aggregation or solution micro-structure. Candidate selection for biopharmaceuticals such has therapeutic antibodies has traditionally focused only on clinical attributes such as target selectivity, in vivo half-life, and other features that may implicitly and inadvertently lead to poor biophysical properties from the perspective of manufacturability and product development. For purposes of selecting therapeutic protein candidates and product formulations, this must be balanced with the need for rapid or high-throughput approaches to allow a large range of candidates to be tested in parallel, as well as to consider both dilute and concentrated protein solutions. Advancements in coarse-grained molecular modeling and algorithms for more rapid / efficient sampling have the potential to make these predictions more routine, while also providing “design rules” that can be implemented without the need for expensive simulations. This seminar focuses on a combination of different levels or scales of molecular modeling, combined with “minimalist” experimental data, and development of design rules based on protein sequence and three-dimensional structures. This includes effects of the product formulation or manufacturing conditions, with an emphasis on antibodies and the importance of complex two-body and multi-body interactions.

Host: Jianing Li

Title: Development of Peptide-Based Probes to Study Cell Signaling in Bacteria

Abstract:
Quorum sensing (QS) is a ubiquitous process in bacteria that governs many important symbiotic and pathogenic phenotypes. As such, QS has attracted considerable attention as a means to control bacterial behaviors - attenuate undesired phenotypes, and promote productive processes. Many Gram-positive bacterial species utilize peptide pheromones to induce QS responses and initiate pathogenic phenotypes, such as competence, biofilm formation and virulence factor production. We investigate the molecular mechanisms that drive signal:receptor binding while interrogating the role of QS in the competition between bacterial species. To this end, we develop peptide-based QS modulators with distinct activity profiles (selective vs. pan-species modulators; inhibitors vs. activators) to test temporal control of QS modulation in both single-species and mixed cultures.

Host: Monika Ivancic

Host: Rory Waterman

Host: Michael Ruggiero

Host: Jose Madalengoitia

Host: Jose Madalengoitia

Host: Matthew Liptak

Host: Jose Madalengoitia

Host: Jose Madalengoitia

Host: Jose Madalengoitia

Host: Michael Ruggiero

Host: Rory Waterman

Host: Matthias Brewer

Host: Matthias Brewer