Interdisciplinary PhD in Structural and Computational Biology and Quantitative Biosciences

Research

Research opportunities in the laboratories of the Biophysics Graduate Degree Program range across many areas at the intersection of the physical, biological and quantitative sciences.

Find below a descriptions of our main areas of interest, and search for research groups that work in these areas.

Biophysical Chemistry

The macromolecules of life acquire a biological activity by folding in three-dimensional space and forming complexes that interact and often influence each-other’s structure and dynamics. Biomolecular interactions, local motions, folding/unfolding transitions and allosteric conformational changes form the basis for the mechanism and regulation of all biological functions. Laboratories focusing on this area of research use a variety of chemical probes and spectroscopic tools to quantitatively understand the rules that govern biological processes in Nature.

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Biotechnology

Research in many laboratories affiliated with the Biophysics program culminates with knowledge that can be transferred onto practically useful products and processes. Biotechnological innovation is critical for the growth and sustainability of essential aspects of everyday life, including health, farming, bio-inspired energy sources and more. Students participating in biotechnology research often go on to embrace successful careers in industry, academia, government laboratories and a variety of private sectors that foster entrepreneurship.

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Computational Biology & Bioinformatics

Computation has revolutionized modern biology. From the powerful analysis of large databases (-omics), to the simulation and design of macromolecular complex, to the application of artificial intelligence methods to solve biological problems, computation is today an intrinsic component of most laboratory research. Many UW-Madison Biophysics groups apply computational methods, often in combination with experimentation, providing outstanding training opportunities cross-disciplinary research. Quantitative-biology groups embracing research at the interface between computational, biological, and physical sciences are in a unique position to handle complex datasets and generate powerful predictive models.

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Membrane and Cellular Biophysics

Cells respond to stimuli and communicate via a variety of molecular and mechanical signals that in turn influence their behavior, differentiation, motility, and shape. To perform functions such as homeostasis, signal transduction, transport, ion conduction, energy production and fusion, cellular membranes host and influence thousands of different proteins embedded within the lipid bilayer. Understanding the properties of these dynamic membrane-biomolecule supramolecular systems is one of the current frontiers of biophysics.

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Microbial Biophysics & Virology

Microbes and viruses are small but incredibly complex. Many of our laboratories employ a variety of biophysical tools to understand specific aspects of the function of bacteria, unicellular eukaryotes, viruses and other members of the microbiome. Understanding the structure, mechanism and regulation of microbial and viral macromolecules is key to answer fundamental questions in biology and their key implications for human health, biotechnology, bio-energy and agriculture.

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Neuroscience

Neurons and neural networks are characterized by an inherent complexity and fascinating aspects whose understanding is still in its infancy. Research group working in this area focus on the structure, function and dynamics of entire neurons and neural subcellular machineries (such as ion channels, receptors, fusion complexes) that control neural transmission and other important biological functions of the brain.

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Personalized Medicine

Recent advances led to the realization that complex organisms are not all created equal. For instance, different human beings have different types and amounts of receptors, metabolites and other important sub- and extra-cellular components. Biophysical approaches to personalized medicine exploit this exquisite diversity at the molecular level and devise novel therapeutic strategies tailored to individual human beings.

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Protein folding, design & function

Proteins are known to curl in three dimensions in the cell, and achieve a shape that is commonly referred to as folding. Protein folding is incredibly important in Nature because folding is a prerequisite for biological function, yet so little is known about it. Research groups engaged in protein folding research explore the mechanisms underlying formation of folded protein structures in vitro, in vivo and in silico. Research in this area is highly cross-disciplinary and it includes the study of folding helpers responsible for ensuring proper folding devoid of aggregation in the cell, including molecular chaperones and the ribosome. Research laboratories in this area also explore links between protein folding and function, and design novel protein sequences tailored to modulate cellular behavior and combat disease.

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RNA/DNA Biophysics

Most aspects of life are encoded in the four-letter code of nucleic acids. Research groups focusing on RNA and DNA biophysics investigate the mechanism by which nucleic-acid coding is generated and regulated at many levels, from nucleic-acid structure and dynamics, chromatin organization, epigenetic modification, transcriptional regulation and protein expression.

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Single Molecule Biophysics

Few microliters of a diluted solution contain trillions of macromolecules. Spectroscopic methods can measure the average (or ensemble) properties of these macromolecules but in many cases, the sheer number of macromolecules in a sample can make measuring specific conformational changes or enzyme activities impossible since different macromolecules are carrying out different reaction steps at the same time. Single molecule methods isolate individual molecules and report binding, conformational changes, and other events as they occur. Techniques, such as single molecule fluorescence, optical trapping, single channel recording, atomic force microscopy, and single particle cryo-EM are extremely powerful for revealing the kinetics, thermodynamics, and structural properties of small proteins and nucleic acids or large supermolecular complexes alike, ultimately providing mechanistic information in unprecedented detail.

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Spectroscopy, Microscopy, Imaging

Spectroscopy and microscopy provide unique “eyes” to watch biomolecules in real time and follow their behavior within a natural environment. Researchers in the UW-Madison Biophysics Graduate Program follow the amazing behavior of biomolecules with innovative spectroscopic and microscopic tools at atomic, molecular, supramolecular and whole-organism level. Techniques highly represented in our program include fluorescence spectroscopy and microscopy, a variety of single-molecule and superresolution approaches, fluorescence anisotropy decay, nuclear magnetic resonance spectroscopy/imaging and nuclear hyperpolarization, circular dichroism, X-ray crystallography, static and dynamic light scattering, X-ray spectro-microscopy, cryo-electron tomography and single-particle cryo-electron microscopy.

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Structural Biology

Structural biology focuses on understanding the molecular framework and bonding patterns that connects atom to generate complex three-dimensional biomolecular structures. Our faculty and students exploit and develop a wide range of techniques to investigate macromolecular structure at high resolution. Our program features outstanding facilities and training opportunities in cryo-electron microscopy, X-ray crystallography, NMR spectroscopy and a variety of other structural-biology techniques. These approaches are routinely applied to understand the structure, dynamics and function of proteins, nucleic acids, membranes, viruses and other complex supramolecular assemblies.

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Synthetic & Systems Biology

System biologists seek to understand the complex dynamics that regulate the function of entire cellular organisms. With the powerful tools of synthetic biology, it is possible to create artificial genetic circuits to manipulate biological organisms for a variety of purposes, including the production of biofuels and the development of novel therapeutics and medical treatments. Students embracing this area of research receive a broad education in the quantitative analysis of cellular genetics and response to stimuli. In addition, this research offers the opportunity to learn how to synergistically combine a variety of tools to manipulate response to stimuli and reprogram cells, thus enabling unprecedented new functions.

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