Department of Chemistry
University of Illinois at Chicago
Chicago IL 60607

Research Overview

Research in the Lorieau group integrates Biophysics, Physical Chemistry, Structural Biology and Biochemistry in elucidating the interplay between biomolecular structure, dynamics, chemistry and function.

With a combination of solution- and solid-state Nuclear Magnetic Resonance spectroscopies, computational tools and other biophysical methods, our research focuses on membrane protein structure and dynamics, membrane protein biochemistry, the development of theory and techniques to enhance the precision and resolution of structural and dynamic information by NMR, and the investigation of molecular dynamics as it relates to enzymatic catalysis and kinetics.

Membranes and Membrane Proteins

Membrane proteins represent approximately a third of expressed proteins in cells, yet they are under-represented in structural databases. We use solution and solid-state NMR to characterize the structures and dynamics of membrane proteins, and the curvature and fusion of membranes.

Viral Infection Proteins and Mechanisms

Influenza, HIV and Ebola viruses have an outer membrane envelope that must fuse with the host cell membrane on cellular entry. We use NMR to characterize the structures and mechanism of viral fusion proteins and the role of membrane curvature.

High-Resolution NMR Methods Development

Solution and solid-state NMR report detailed information on the distribution of electrons, the distances between atoms and the dynamics of molecules at the atomic level. We investigate new methods to increase the resolution of NMR structures, molecular dynamics and the distribution of conformation ensembles.
News December 07, 2017

Congratulations to Dr. Adrian Draney

Adrian Draney Congratulations to Adrian Draney on earning his PhD! Dr. Draney is the second member of the Lorieau group to receive his PhD. He will join the laboratory of Prof. Guido Pintacuda at the Ecole normale supérieure de Lyon to conduct solid-state NMR experiments.

News November 16, 2017

New Members Zoe Petros and Alec Malooley

Zoe Petros Alec
Malooley Welcome to Zoe Petros and Alec Malooley, the newest graduate student members of the Lorieau group. Zoe joins us from the University of Illinois, Urbana-Champaign and Alec comes from the University of Illinois, Chicago. They will be working on membrane protein structures by NMR.

News November 04, 2017

Congratulations to Dr. Sean Smrt

Sean Smrt Congratulations to Sean Smrt on earning his PhD! Dr. Smrt is the first member of the Lorieau group to receive his PhD. He will join the laboratory of Prof. Tim Cross at the National High Magnetic Field Laboratory at Florida State University to conduct solid-state NMR experiments on the membrane proteins of Mycobacterium tuberculosis.

Publication October 15, 2017

Mollib: a molecular and NMR data analysis software

Citation: Lorieau JL. (2017) Mollib: a molecular and NMR data analysis software. J. Biomol. NMR. 69(2): 69-80. doi: 10.1007/s10858-017-0142-5.

Mollib is a software framework for the analysis of molecular structures, properties and data with an emphasis on data collected by NMR. It uses an open source model and a plugin framework to promote community-driven development of new and enhanced features. Mollib includes tools for the automatic retrieval and caching of protein databank (PDB) structures, the hydrogenation of biomolecules, the analysis of backbone dihedral angles and hydrogen bonds, and the fitting of residual dipolar coupling (RDC) and residual anisotropic chemical shift (RACS) data. In this article, we release version 1.0 of mollib and demonstrate its application to common molecular and NMR data analyses.

Publication September 15, 2017

Structure and Dynamics of Membrane Proteins and Membrane Associated Proteins with Native Bicelles from Eukaryotic Tissues

Citation: Smrt ST, Draney AW, Singaram I, Lorieau JL. (2017) Structure and Dynamics of Membrane Proteins and Membrane Associated Proteins with Native Bicelles from Eukaryotic Tissues. Biochemistry. 56(40): 5318-5327. doi: 10.1021/acs.biochem.7b00575.

biochem toc In vitro studies of protein structure, function and dynamics typically preclude the complex range of molecular interactions found in living tissues. In vivo studies elucidate these complex relationships, yet they are typically incompatible with the extensive and controlled biophysical experiments available in vitro. We present an alternative approach by extracting membranes from eukaryotic tissues to produce native bicelles to capture the rich and complex molecular environment of in vivo studies while retaining the advantages of in vitro experiments. Native bicelles derived from chicken egg or mouse cerebrum tissues contain a rich composition of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA), lysolipids, cholesterol, ceramides (CM) and sphingomyelin (SM). The bicelles also contain source-specific lipids such as triacylglycerides (TAGs) and sulfatides from egg and brain tissues, respectively. With the influenza hemagglutinin fusion peptide (HAfp) and the C-terminal Src Homology domain of Lymphocyte-specific protein-tyrosine kinase (lck-cSH2), we show that membrane proteins and membrane associated proteins reconstituted in native bicelles produce high-resolution NMR data and probe native protein-lipid interactions.

Publication March 13, 2017

Hybrid NMR: A Union of Solution- and Solid-State NMR

Citation: Thiagarajan-Rosenkranz P, Draney AW, Lorieau JL. (2017) Hybrid NMR: A Union of Solution- and Solid-State NMR. J. Am. Chem. Soc. 139(13): 4715-4723. doi: 10.1021/jacs.6b11402.

jacs toc Hybrid NMR (hdNMR) is a powerful new tool that combines the strengths of solution- and solid-state NMR to measure dipolar, chemical shift, and quadrupolar tensors in aqueous solution. We introduce the theory of hdNMR and partially randomly oriented (PRO) crystalline hydrogel samples. PRO samples produce randomly oriented spectra with characteristic Pake patterns from the solid state, yet they maintain the high-resolution dispersion of solution NMR experiments. With new pulse sequences, we show how hdNMR can be used to measure with high precision the 1Hα13Cα dipolar tensor and carboxylate chemical shift anisotropy tensor of aspartate. These measurements contain detailed information on the distribution of electron density, interatomic distances, and the orientation dependence of molecular motion.

News February 01, 2017

NSF CAREER Awarded to the Lorieau Group

group photo The Lorieau group received the CAREER award from the National Science Foundation (NSF) for the project titled, “CAREER: Mechanism of Protein Catalyzed Membrane Fusion.” This project investigates the molecular mechanism of viral infection in the influenza virus and other related viral systems. News coverage on the grant can be found here. (Photo: UIC/Jenny Fontaine)

Publication December 14, 2016

Membrane Fusion and Infection of the Influenza Hemagglutinin (Chapter)

Citation: Smrt ST, Lorieau JL. (2016) Membrane Fusion and Infection of the Influenza Hemagglutinin (Chapter). Adv. Exp. Med. Biol. (Springer): 1-18. doi: 10.1007/5584_2016_174.

The influenza virus is a major health concern associated with an estimated 5000 to 30,000 deaths every year (Reed et al. 2015) and a significant economic impact with the development of treatments, vaccinations and research (Molinari et al. 2007). The entirety of the influenza genome is comprised of only eleven coding genes. An enormous degree of variation in non-conserved regions leads to significant challenges in the development of inclusive inhibitors for treatment. The fusion peptide domain of the influenza A hemagglutinin (HA) is a promising candidate for treatment since it is one of the most highly conserved sequences in the influenza genome (Heiny et al. 2007), and it is vital to the viral life cycle. Hemagglutinin is a class I viral fusion protein that catalyzes the membrane fusion process during cellular entry and infection. Impediment of the hemagglutinin’s function, either through incomplete post-translational processing (Klenk et al. 1975; Lazarowitz and Choppin 1975) or through mutations (Cross et al. 2001), leads to non-infective virus particles. This review will investigate current research on the role of hemagglutinin in the virus life cycle, its structural biology and mechanism as well as the central role of the hemagglutinin fusion peptide (HAfp) to influenza membrane fusion and infection.