Research opportunities in IPiB laboratories range across many areas of biochemistry and intersect with other disciplines in biological, chemical, and physical sciences. Our main areas of interest are described below.
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Research Areas
Biomolecular Folding and Interactions
Inside the cell, proteins and nucleic acids never exist in isolation. Complexes between biomolecules are essential for a variety of cellular functions. In some cases, complexes are formed transiently as in the case of chaperones that help proteins fold or proteins that target biomolecules for degradation. In other cases, these complexes are exquisitely specific and form tight interactions that can last for days. IPiB faculty approach the problems of how biomolecules fold and interact with one another using a variety of approaches including genetics, structural biology, biophysics, and chemical probing.
Cell Structure and Signalling
Cells respond to and communicate with a variety of chemical, molecular and mechanical signals that can influence cell identity, mitosis, differentiation, motility, and shape. Since every cell behavior is tied to cues that emanate from the environment or originate within the cell itself, it is critical to understand the mechanisms of cell signaling. Key players in this process are the components of the cell or the cell structure. How cell structure and function are coordinated to respond to a signaling event and modify cell activity remains an open and fascinating area of research.
Chemical Biology and Enzymology
Chemistry can add a powerful dimension to the study of biological systems. Small molecules, peptides, proteins, polymers, and biocompatible materials have enabled IPiB faculty at UW-Madison to interrogate biological molecules, cells, and multicellular organisms spatially, temporally, and reversibly. Chemical Biology on the UW-Madison campus has a rich history that extends back to the Enzyme Institute and has been fueled by an on-going NIH training grant program (Chemistry and Biology Interface Training Grant) funded since 1993, as well as the establishment of a cluster hire initiative in chemical biology across campus.
Developmental Biology
In a developing organism, many different cellular and molecular events are orchestrated to generate a functional plant or animal. Any deviation from the normal developmental plan can result in mutant tissue that may harm the adult organism. During development, dynamic changes in gene expression influence cell fate and differentiation, while at the same time signaling between cells further shapes cell and tissue growth. Development can be viewed as a cellular “dance” in which cells establish the connections and networks of communication that often last a lifetime.
DNA Metabolism and Genome Maintenance
The genome is perhaps life’s greatest achievement. Packaged within a four letter code is life’s instruction manual. It is now clear that this manual is subject to enormous degree of regulation at the level of chromatin organization, nucleosome positioning and modification, as well as epigenetic modification of the nucleic acids themselves. When a cell divides, this genome must be efficiently and accurately copied. When a cell is exposed to mutagenic attack, the genome must be protected and repaired.
Gene Expression and RNA Biology
The transcript is essential for the genome to convey its information to the world. The RNAs produced by transcription can have an enormous array of potential functions. Some RNAs encode messages that will be translated into proteins. Other RNAs become processed into small fragments that are essential for cellular regulation. Yet others may possess catalytic activity and form core components of cellular machines such as the ribosome and spliceosome. Understanding RNA biochemistry, the many roles of RNA in the cell, and how RNA transcripts can be modified and subject to regulation is essential for understanding life itself.
Immunology and Virology
Viruses and the immune system are both masters of economy and microcosms for studying biochemistry. Viruses pack precisely the right amount of genetic information into a capsid to subvert a cellular target’s biochemistry. The immune system, on the other hand, can respond to nearly any external, infectious agent and remember those responses for decades. In humans, viral infections and the immune system are engaged in a molecular war with profound consequences for our health.
Membrane Dynamics and Proteins
Understanding the dynamic organization of membranes, mechanisms that regulate membrane fusion, rules that regulate membrane protein localization, and the biophysical principles that govern membrane protein structure and function are among the most challenging and pressing questions at the frontiers of current biology.
Metabolism and Endocrinology
Metabolic disorders including obesity, diabetes, hypertension and atherosclerotic heart disease are among the most prominent and costly conditions affecting people worldwide. It is becoming clear that these and other common diseases result from alterations in both classic and newly defined metabolic pathways. IPiB laboratories are leveraging a wide array of techniques, ranging from mass spectrometry-based proteomics and metabolomics to organismal physiology and genetics, to explore these problems and their molecular underpinnings.
Metals in Biology
Metals play important roles in a wide range of biological processes. Biochemistry laboratories investigating metallobiology harness spectroscopic, computational, biochemical, and microbiological techniques to study metal transfer, protein-protein interactions, and more.
Quantitative Biology
Quantitative biology is the interface of computational, biological, and physical sciences that elaborates complex datasets into quantitative and predictive models. Many IPiB laboratories integrate computational techniques and wet-lab experiments (often in high-throughput) to understand the rules that govern the function of many biological systems.
Structural Biology
Structural biology is focused on providing a molecular framework that connects atoms to biology. Our faculty use a wide range of techniques to investigate macromolecular structure, including cryo-electron microscopy, X-ray crystallography and NMR spectroscopy to understand the structure and function of enzymes, membrane proteins, redox proteins, molecular machines, nucleic acid complexes and other important biomolecules.
Systems and Synthetic Biology
Synthetic biologists seek to create artificial genetic circuits to manipulate biological organisms for a variety of purposes, including for the production of biofuels and for providing new medical treatments and therapeutics. IPiB students will receive a broad education in quantitative analysis of cellular genetics and responses to stimuli, as well as how to use tools from a variety of disciplines to manipulate these responses to achieve novel functions.