The Department of Biochemistry explores diverse research questions using a wide variety of approaches, experimental systems, and techniques. Through extensive cross-fertilization, faculty, students and postdoctoral fellows alike are aware of everyone’s research and are bonded by a central interest in understanding fundamental biological questions at the level of how molecules act and interact to accomplish highly complex, intra- and intercellular processes. Research in molecular medicine and connections to clinical research groups are commonplace.
Explore the labs
We invented a device that measures ammonia from a small drop of blood, and are now testing it with patients. Rapid diagnosis will prevent brain damage in patients with dysfunctional urea cycles due to genetic mutation, liver dysfunction, or cancer chemotherapy.
We are studying the megadalton protein complex that catalyzes DNA double-strand break repair pathway of nonhomologous end joining.
Rhiju Das's research group strives to predict how sequence codes for structure in proteins, nucleic acids, and heteropolymers whose folds have yet to be explored. The Das lab uses new computational and experimental tools to tackle the de novo modeling of protein and RNA folds, the high-throughput structure mapping of riboswitches and random RNAs, and the design of self-knotting and self-crystallizing nucleic acids.
Ron Davis' research group is using Saccharomyces cerevisiae and Human to conduct whole genome analysis projects. The yeast genome sequence has approximately 6,000 genes. The Davis group has made a set of haploid and diploid strains (21,000) containing a complete deletion of each gene. In order to facilitate whole genome analysis each deletion is molecularly tagged with a unique 20-mer DNA sequence. This sequence acts as a molecular bar code and makes it easy to identify the presence of each deletion.
The Ferrell Lab is studying several biological processes, including cell cycle regulation, apoptosis, and cellular organization. We draw upon a combination of quantitative experimental approaches, computational modeling, and the theory of nonlinear dynamics. Our goal is to understand the circuits that allow cells to make reliable decisions, and how these decisions propagate in both space and time.
The Harbury lab aims to measure and understand dynamic structural changes in proteins, and their role in the functional biology of macromolecular machines. We are developing tools to determine 3D protein structures and to detect structural fluctuationsin situ: directly inside cells and in complex reconstituted systems. A second objective is to genetically map chemical space and exploit it for the discovery of tailored small molecules. We have created a technology that reenacts billions of years of natural product evolution in a test tube. More generally, we explore innovative experimental approaches to problems in molecular biochemistry, focusing on technologies with the potential for broad impact.
The Herschlag group's research is aimed at understanding the chemical and physical behavior underlying biological macromolecules and systems, behaviors that define the capabilities and limitations of biology. Toward this end we use multidisciplinary approaches to understand how RNA and protein enzymes assemble active sites and achieve their enormous catalytic power and exquisite specificity; we are developing a quantitative and predictive understanding of RNA folding; and we are uncovering the rules that determine RNA/protein interactions in vitro and in vivo. Our research has broad implications for evolution and function of RNA and proteins and for how RNA/protein interactions regulate gene expression.
Research interests in the Khosla Laboratory lie at the interface of chemistry and medicine. For the past several years, the lab has investigated the catalytic mechanisms of modular megasynthases such as polyketides synthases, with the concomitant of harnessing their programmable chemistry for preparing new antibiotics. More recently, the group has investigated the pathogenesis of celiac sprue, an HLA-DQ2 associated autoimmune disease of the small intestine.
We are studying the mechanism of viral membrane fusion and its inhibition by drugs and antibodies. We use the HIV envelope protein (gp120/gp41) as a model system. Some of our studies are aimed at creating an HIV vaccine that elicits antibodies against a transient, but vulnerable, intermediate in the membrane-fusion process, called the pre-hairpin intermediate. We are also interested in protein surfaces that are referred to as “non-druggable”. These surfaces are defined empirically based on failure to identify small, drug-like molecules that bind to them with high affinity and specificity. Some of our efforts are aimed at characterizing select non-druggable targets. We are also interested in developing methods to identify ligands for non-druggable protein surfaces.
The Krasnow Lab uses genetic and genomic approaches to elucidate, at single-cell resolution, the genetic programs that control development, renewal, and regeneration of the lung. We are especially interested in stem cells and how their behaviors are controlled in three dimensions to generate functional tissue, and in using this information to understand and treat lung disease and to regenerate a lung. We use similar approaches to map the breathing pacemaker and neural circuit of breathing and to identify breathing arrhythmias.
We use chemical biology to uncover biochemical mechanisms in innate immunity and, in parallel, develop therapeutic hypotheses and lead compounds. Innate immune pathways as the first line of defense against pathogens present many exciting opportunities for chemical biologists. These pathways are a rich source of novel chemistry: they involve diverse molecular patterns in pathogens, little-explored second messengers, and drugs with poorly understood mechanism. Activation of innate immunity is a proven therapeutic strategy for vaccination, viral infection, and cancer, while inhibition is a strategy for treating autoimmune diseases and sterile inflammation. To date, however, most modulators of innate immunity are broad, non-specific, and poorly characterized, such as killed bacteria, alum crystals, and steroids.
The Long Laboratory studies the early stages of symbiosis between Rhizobium (also Sinorhizobium) meliloti and and its host plants in the genus Medicago. The symbiosis is uniquely approachable by experiment because each partner can be genetically manipulated, and transgenic organs can be constructed, allowing highly specific genetic tests of various components of signal and response. The lab uses genetics, biochemistry and cell biological approaches to study how cell division, growth, and gene expression arise in each partner due to stimulation from the other.
The goal of research in the Pfeffer Lab is to elucidate the molecular mechanisms by which receptors are transported between specific membrane compartments in cells and how LDL derived cholesterol is exported from lysosomes. We are pioneers in the study of Rab GTPases that are master regulators of receptor trafficking. Rab GTPase phosphorylation by the LRRK2 kinase was recently linked to familial Parkinson’s Disease. We have discovered a Hedgehog signaling pathway that is blocked in specific neurons in the brain upon Rab phosphorylation, and we are testing a model that may explain in molecular detail, how this event leads to Parkinson’s Disease.
The Rohatgi Lab is working to elucidate the biochemical and cell biological principles that govern signaling pathways that sit at the intersection between developmental biology and cancer. Their toolkit combines bulk biochemical techniques, such as cell-free reconstitution, with microscopy using novel optical probes to study the dynamics of signal propagation in cells. The group strives to develop novel strategies for the manipulation of these pathways for cancer therapies and applications in regenerative medicine.
Our goal is to develop statistical and experimental tools to construct a high dimensional picture of gene regulation, including cis and trans control of the full repertoire of RNAs expressed by cells. Currently, we are studying the function and biogenesis of circular RNA, which we recently discovered to be a ubiquitous and uncharacterized component of eukaryotic gene expression. A second major goal is to study gene expression variation in human cancer. Using massive public datasets and primary tumors, we develop new bioinformatic and statistical tools and test models. We use the cancer genome as window into functional roles played by RNA, and are attempting to characterize potential biomarkers.
Over the last several decades the Spudich laboratory studied the structure and function of the myosin family of molecular motors in vitro and in vivo, and we developed multiple new tools, including in vitro motility assays taken to the single molecule level using laser traps. That work led us to our current focus on the human cardiac sarcomere and the molecular basis of hypertrophic and dilated cardiomyopathy. We postulated in 2015 that a majority of hypertrophic cardiomyopathy mutations are likely to be shifting b-cardiac myosin heads from a sequestered off-state to an active on-state for interaction with actin, resulting in the hypercontractility seen clinically in hypertrophic cardiomyopathy patients. This hypothesis is different from earlier prevailing views, and this viewing an old disease in a new light is the basis of our current research.
The Straight Group studies the process of cell division in eukaryotes focusing on the mechanisms of chromosome segregation. Their research utilizes biophysical, biochemical, microscopic and cell biological approaches in systems ranging from yeasts and flies to frogs and humans. Their goal is to understand, at a molecular level, the principles of chromosome organization and segregation that ensure genome stability during cell division and differentiation.
My research focuses on the apicoplast, a prokaryotically-derived plastid organelle unique to Plasmodium (and other pathogenic Apicomplexa parasites) and a key anti-malarial drug target. My laboratory's goal is to elucidate apicoplast biology, function, and role in pathogenesis with the ultimate goal of realizing the potential of the apicoplast as a therapeutic target.