Representative Faculty Research Projects
Overview:
One of the unique features of the CBB program at Northwestern University is the student's opportunity to work on a research project in a streamlined curriculum.
Gregory Beitel (Biochemistry, Molecular Biology, & Cell Biology) EV
Elevated CO2 levels in the lungs and blood stream (hypercapnia) is present in about 40% of the >350,000 patients hospitalized by chronic obstruct pulmonary disease (COPD) each year. Currently COPD is the fourth leading cause of death in the US, exceeded only by cancer, heart disease and stroke. The cellular pathways that sense and respond to CO2 in non-neuronal cells have not been defined in any system, but a collaboration between the Beitel lab (BMBCB, Evanston) and the Sporn lab (Pulmonary and Critical Care lab, Feinberg School of Medicine, Chicago) has shown that in both Drosophila and vertebrate immune cells, the induction of host defense genes downstream of the NFkB-family of transcription factors is impaired by elevated CO2 levels. Responses are down-regulated five to several hundred fold. Both groups have used genome wide microarray analysis to identify specific sets of genes that are regulated by CO2 that are distinct from genes regulated by hypoxia or environmental stress. In Drosophila we identified a 2.2 kb promotor element that is regulated identically to the endogenous gene by CO2 when placed in the contest of a luciferase-reporter construct. For a variety of reasons, we hypothesize that the CO2 regulation is exerted via transcriptional effects on individual immune response genes. Further, we propose that analogously to the oxygen-sensing HIF pathway, that there will be a specific DNA response element to which binds a CO2-regulated transcriptional factor or complex. Given that we have genes sets of genes that are regulated or not by CO2, and a 2.2kb genomic fragment that definitely does confer CO2-responsiveness, it should be possible to use bioinformatics to identify sequence elements that are unique to CO2-regulated genes and that could be CO2-response elements. Predicted sites could easily be mutated in the 2.2 kb reporter gene to determine if such sites are required to mediate CO2 responses. We envision this project as a joint project between the Beitel/Sporn labs and a bioinformatics lab such as Dr. Papoutsakis’ or Dr. Amaral's. A bioinformatics student would do the in silico sequence analyses, and could if they were interested continue the project to do the "wet" cell biologic tests of any resulting bioinformatic predicts. If a student were only interested in the in silico analyses; that would be fine as other students in the Betiel lab would be happy to do the wet tests.
Rex Chisholm (Center for Genetic Medicine) CH
Myosins are a class of molecular motors that interact with actin to power cell motility and facilitate a wide range of processes ranging from intracellular transport to cardiac and skeletal muscle contraction. Myosin motors have been linked to numerous human diseases, including hypertrophic cardiomyopathy, the leading cause of sudden death in otherwise healthy adults. Dr. Chisholm studies myosin proteins and is also the Principal Investigator for the dictyBase resource, a development platform of a genome database for Dictyostelium discoideum, a NIH-supported model organism. dictyBase provides integrated access to the annotated Dictyostelium genome sequence, curated literature, and functional genomics data through their website. Daniel Schneider, a part-time CBB student, works with Dr. Chisholm and Dr. Kibbe on the dictyBase project.
Ann Harris (Pediatrics) CH
Regulation of expression of the CFTR gene, which when mutated causes Cystic Fibrosis, is complex and poorly understood. The CFTR mRNA and protein show patterns of expression in vivo that are tightly regulated both temporally, during development, and spatially in different tissues. However, elements in the basal promoter do not confer accurate temporal and spatial expression on transgenes and very little is known about other regulatory elements that confer tissue specificity on CFTR expression. We have generated data over the past several years that implicate intronic sequences in tissue specific regulation of CFTR expression. The sequences are located many kilobases away from the basal promoter; hence, it is important to establish their mechanism of action within chromatin and how they influence gene expression. We propose to utilize bioinformatic approaches to interrogate individual regulatory elements and their combined role in global regulation of CFTR chromatin structure.Aggelos Katsaggelos (Electrical Engineering & Computer Science) EV
Dr. Katsaggelos and Dr. Sotirios Tsaftaris are interested in the analysis of signal processing for bioinformatics-related research. Dr. Tsaftaris spearheads a
project called
″Signal Processing and Biology Meet at IVPL (Image and Video Processing Laboratory)″.
Andreas Matoushek (Biochemistry, Molecular Biology, & Cell Biology) EV
Dr. Matoushek is interested in the mechanisms of macromolecular machines, particularly the mechanism by which proteins are unfolded by translocases and proteases.
Richard Morimoto (Biochemistry, Molecular Biology, & Cell Biology) EV
Dr. Morimoto and the members of his laboratory are interested primarily in "Chaperone Networks and Mechanisms of Protein Conformational Disease". Vanessa Wereko, CBB ’06, was the first student to graduate from the CBB Program and did her MS research in Dr. Morimoto's laboratory.
Ishwar Radhakrishnan (Biochemistry, Molecular Biology, & Cell Biology) EV
Research in the Radhakrishnan lab is directed towards clarifying the basis for how proteins function in the cell, with a particular emphasis on the sequence and structural requirements that govern non-covalent interactions with other biomolecules. This research combines traditional experimental approaches with informatics approaches. Central to the informatics endeavors is the development and application of computational tools to mine sequence and high-resolution structural data. One such tool that we have developed in the lab is called MONSTER. Extensions to this tool are envisaged including integration with complementary tools to facilitate higher-order analyses of biomolecular complexes including automatic detection of complex motifs and patterns and structure prediction of novel interacting proteins/biomolecules.
Denise Scholtens (Preventive Medicine) CH
Dr. Scholtens is currently developing methodology for the analysis of high-dimensional data, the analysis of factorial designed microarray experiments and local modeling of protein complexes.
Hans-Georg Simon (Pediatrics) CH
The Simon laboratory is interested in the formation of the emergence of biological information. The laboratory uses a range of molecular techniques to clone and engineer genes, biochemical techniques to determine the encoded protein structure and function, cell biological techniques to visualize subcellular localizations of mRNA and protein, and bioinformatics to identify gene pathway association and regulation. For functionally testing gene in vivo, we are employing retroviral gene-transfer, antisense knock-down, and genetic knock-out approaches.
Joshua Singer (Neurobiology) CH
Retinal Microcircuitry: Night vision represents a remarkable feat of signal processing: the absorption of only a few photons by an array of thousands of rod photoreceptors somehow generates a visual response. In mammals, a specialized collection of interneurons transfers rod signals to ganglion cells, the output cells of the retina; this microcircuit is called the rod pathway. The rod pathway is anatomically well-characterized, but little is known about the nature of signal transfer between its component neurons. In particular, we do not understand how the signal generated by rod photoreceptors is passed across multiple synapses (both chemical and electrical) without being contaminated and degraded by synaptic noise. My laboratory addresses this issue by studying the physiology of the interneurons in the rod pathway: specifically, rod bipolar cells and AII amacrine cells. Most of the experiments we perform involve electrical recordings from visually identified neurons in a mammalian retinal slice preparation. These recordings have allowed us to study the membrane properties of rod bipolars and AII amacrines as well as chemical synaptic transmission between rod bipolars and AIIs and electrical coupling between AIIs. Recently, we have become interested in integrating computational models into our studies. These models will be generated in the NEURON programming environment and will be constrained by morphological and electrophysiological data acquired by our laboratory. Specifically, we would like to examine signal processing by groups of electrically coupled AII amacrine cells to understand how the rod pathway maintains the high signal-to-noise ratio required for night vision and how it is optimized to encode small rod signals with a great degree of reproducibility.
D. Martin Watterson (Molecular Pharmacology & Biological Chemistry) CH
The laboratory uses an interdisciplinary approach to study fundamental biological processes and mechanisms of pathophysiology. His laboratory has identified new approaches to therapeutic intervention in areas of unmet medical need, the approach centers around integrative chemical biology, medicinal chemistry, and computational biology interdigitated with molecular genetics and animal models of disease. IGP PhD candidate and CBB student Laura Wing works with Dr. Watterson.
Patrick C. M. Wong (Communication Sciences and Disorders) EV
1.To develop and compare computational tools for characterizing networks of cortical activation measured by fMRI (e.g., multivariate methods, graph theory).
2.To use computational methods for comparing networks of cortical activation associated with different auditory tasks (e.g., identification of musical styles, perception of native and foreign speech sounds) and different auditory skill levels (e.g., musicians vs. nonmusicians).
3.To use computational methods for examining changes in cortical networks as adults acquire new auditory skills (e.g., learning a foreign language) and to use such methods for evaluating training efficacy.
4.To perform automated speech (or other auditory object) recognition based on multivoxel pattern analysis of fMRI brain activation data (e.g., by looking at brain activation patterns, we can tell whether the human subject is perceiving an [r] sound), and to use such method for objectively evaluating success in acquiring new speech perception skills.
5.To develop and compare computational tools for linking neurophysiologic data acquired using different neuroimaging methods; in particular, auditory brainstem responses using ERP (good temporal resolution) and cortical responses using fMRI (good spatial resolution).
6.To develop and assess procedures for measuring brain activity (fMRI BOLD signal) in regions of the brain that are most susceptible to artifacts (e.g., temporal lobe, brainstem nuclei).
7.To develop automated procedures for measuring the size and morphology of brain structures and to associate such findings with individuals with different auditory skill levels; for example, certain structures are larger in musicians. [Currently, in order to measure the size of a specific brain structure, e.g., the Heschl’s Gyrus, manual procedures are used.]
8.To develop algorithms for automatically recognizing pitch and intonation of talkers of different genders and speaking styles. [Not directly related to MRI but a side project which would help review how speech processing occurs and can be used commercially.]
CH = Chicago campus; EV = Evanston campus
The Program in Computational Biology and Bioinformatics has been suspended and no further admission activity will take place, effective in the summer of 2008.
Bruce A. Lindvall, Ph.D.
Assistant Dean for Graduate Studies
McCormick School of Engineering and Applied Science
Phone 847-491-4547
To send email to Dr. Lindvall, click here