With the support of The Paul G. Allen Family Foundation, Dr. Neil Kelleher will be further exploring how human blood cells – B-cells – mature from their beginnings in our bone marrow to those that protect us from infection. Kelleher will focus on scanning and mapping the B-cell development process and how deviations can result in cancers like leukemia and multiple myeloma. By mapping this process at a high resolution, Kelleher will develop a protocol to identify markers and rules for defining cell types and their relationships, and in doing so further the understanding of human wellness and disease.

Neurons become vulnerable when they fail to maintain cellular homeostasis, which require very complex dynamics of protein-protein interactions. We think that understanding neuronal vulnerability requires investigation of protein landscape of neurons that begin to show signs of degeneration at a cellular level. Previously, it was impossible to investigate the protein content of distinct neuron populations because they are very limited in numbers and the proteomics approaches were not sensitive enough to detect low levels of proteins. Today we are at the crossroad of important discoveries; we now can: 1) isolate pure populations of both healthy and diseased upper motor neurons at different disease stages; 2) determine protein content within pure neuron populations with high precision using top-down, bottom-up proteomics; 3) determine protein-protein interactions that are critically important for neuron function; 4) using well-defined model systems we can test biology-derived and well-educated hypotheses. Our unique strengths, when combined, overcome limitations in the field and allow identification of protein dynamics in vulnerable and degenerating neurons. This information sets the stage for many important discoveries to come, and could potentially identify candidate early detection markers especially for diseases in which upper motor neurons are affected, such as ALS.

Reactivation of latent Cytomegalovirus (CMV) remains an important clinical problem following transplantation with two recent developments forming the basis for this proposal: first, a central mechanistic theme has emerged from in vitro and in vivo studies of HCMV and MCMV respectively; and second, the current paradigm of transplantation is shifting towards donor-specific tolerance. Together, these developments call for integration of molecular mechanistic insights from diverse models and reactivation, and an exploration of uncharted waters regarding how CMV might behave in tolerant recipients. Three separate but inter-related projects, and three supporting cores in a collaborative research initiative designed to accelerate the development of potential therapeutic strategies to prevent, rather than treat CMV reactivation.

Protein complexes are cellular machines that manage and perform most functions in our cells and in all living organisms. Scientists continue to struggle to understand their composition, their structure and how they can malfunction. Because the most revealing and accurate approach—examining native complexes as entire units—has seemed virtually impossible, most analyses have used mass spectrometry of protein fragments, which may lead to partial or misleading results. A team from Northwestern University, in collaboration with Thermo Fisher Scientific, plans to overcome this major barrier in disease research by developing a new kind of mass spectrometer that combines the advantages of Time-of-Flight (TOF) and Fourier Transform (FT) analyzers. This instrument will be used to separate an intact protein complex from a mixture and then detect it directly or activate to release its subunits. The instrument will then detect the intact masses of subunits and the fragmentation products that result from their stepwise disassembly. To this platform, they will couple new separation strategies and software, followed by application of the combined system to mitochondrial complexes isolated from models of aging and kidney cancer. This integrated workflow will constitute a major advance in protein mass spectrometry, accelerate the understanding of disease at a molecular level and address a key challenge of this century: to define the human proteome.

We are members of the The Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling at the University of Illinois at Urbana-Champaign. If you have a project which relates to the study of addiction mechanisms in the central nervous system, please contact the center at the link below. The Center is built around the overarching theme of cell to cell signaling, integrating research groups with expertise in the fields of analytical chemistry and bioinformatics with those in biological and behavioral neuroscience in a unified, directed approach to discovery of the intricacies of intercellular signaling.

Visit the website: The Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling.