ROSETTACOMMONS - Key Persons
Job Titles:
- Director
- Documentation Chair
The DeGrado lab works on the design of proteins and small molecules to address problems of biomedical interest.
The Correia Group is driven by the passion of expanding nature's repertoire by designing novel functional proteins to be used for practical purposes such as therapeutics, vaccines, biosensors and others.
The Smith Lab aims to determine the atomic-level mechanisms of how changes in the so-called "second shell" and beyond propagate through the protein and ultimately affect function. This can enable protein activity to be regulated by distant events through a process called allostery. Furthermore, deleterious mutations far removed from the active site make the protein malfunction and cause disease. In other cases, protein engineering has discovered unusually located mutations that enhance activity, making synthetic and therapeutic applications possible. The common mechanistic question about these examples is the following: how do atomic rearrangements propagate from one part of the structure to another? Even more intriguingly, how can a signal propagate without distinct structural changes? There are an increasing number of cases where this communication happens not through a change in the structure of the protein, but in the amount of motion.
The Kulp lab focuses on rational vaccine and therapeutic antibody design for a variety of NIAID priority infectious diseases (e.g. Lassa Virus) and cancer targets. The ultimate test of our understanding of B cell immune responses is to design new immunogens that drive predictable antibody maturation. To that end, we are interested in the development and application of protein engineering methods for modifying antigen/cell receptor interfaces, antigen/antibody interfaces, antigen surface properties and core stabilization.
The primary goals of the research in the Baker group over the past several years have been to predict the structures of naturally occurring biomolecules and interactions and to design new molecules with new and useful functions. These prediction and design challenges have direct relevance for biomedicine and provide stringent and objective tests of our understanding of the fundamental underpinnings of molecular biology.
To carry out the prediction and design calculations, we have been developing a computer program called Rosetta. At the core of Rosetta are potential functions for computing the energies of interactions within and between macromolecules, and methods for finding the lowest energy structure for a protein or RNA sequence (structure prediction) and for finding the lowest energy sequence for a protein or given structure or function (design) (Das and Baker, 2008). Feedback from the prediction and design tests is used continually to improve the potential functions and the search algorithms. Development of one computer program to treat these diverse problems has considerable advantages: first, the different applications provide complementary tests of the underlying physical model (the fundamental physics/physical chemistry is, of course, the same in all cases); second, many problems of current interest, such as flexible backbone protein design and protein-protein docking with backbone flexibility, involve a combination of the different optimization methods.
Job Titles:
- MIGAL - Galilee Research Institute
The main objective of research in the Fischer lab has been to understand the mechanisms by which cells control protein stability, and to develop novel therapeutic strategies that modulate protein stability. We combine a broad range of technologies from structural biology, biochemistry, cell biology to large scale multi-omics and computational methods.
The Ubiquitin Proteasome System is involved in virtually any cellular process and frequently implicated in human diseases. The Fischer lab combines structural biology, cell biology, and high throughput biology approaches to understand the mechanistic principles that govern signaling through the ubiquitin proteasome system. We leverage these insights to propose and test new avenues of therapeutic intervention, such as targeted protein degradation or SPLiNTs. Our work has contributed to the now widespread application of targeted protein degradation in drug development and as a powerful tool to study biology.
The Procko lab uses the tools of directed evolution to inform computational modeling of transmembrane proteins. We are particularly interested in G protein-coupled receptors with large extracellular domains for the recognition of small molecule ligands. Such receptors are abundantly expressed in the nervous system for the detection of neurotransmitters, pheromones, and sweet or savory tasting substances. The structures of individual domains for these receptors are known, but how they are arranged in a full receptor is unclear. We are developing experimental methods to map the sequence-fitness landscape of these receptors, which can be used to constrain conformational sampling during structure prediction of resting or active states.
Job Titles:
- Director
- Confrence Executive Chair
Job Titles:
- Cancer Research Center / Rensselaer Polytechnic Institute
The Corn Lab develops and uses next-generation genome editing and regulation technologies. We work on both fundamental biological discovery and potential therapies for human genetic diseases. Our focus is the mechanisms by which cells repair their DNA, maintain and differentiate hematopoietic stem cells, and use ubiquitin signaling to propagate cellular signals. Through technology development, mechanistic cellular biochemistry, and translational projects, we are working to unravel complex cellular phenotypes to further biological understanding and improve human health.
Job Titles:
- Director
- Early Career Faculty Chair
Job Titles:
- Business Development Chair
Jiang lab focuses on computational structural biology and drug design for Alzheimer's, Parkinson's, Lou Gehrig's disease and other degenerative disorders. Current research is driven by two key questions: How do unfolded or misfolded proteins self-associate into abnormal aggregates? How do these aggregates propagate and lead to disease? Ongoing research is to develop new therapeutic approach for neurodegenerative and other brain diseases, which includes: 1) design allosteric BACE inhibitor that specifically blocks the APP cleavage and Abeta production; 2) design protein inhibitor that blocks the prion-like transmission of protein aggregates in neurodegenerative diseases; 3) design and test new protein that crosses the blood-brain barrier via carrier-mediated transport. The findings of the research will identify new drug targets, develop new therapeutics and design new therapeutic compounds or peptides for the treatment of neurodegenerative disorders. All of these will strengthen our ability of designing biological systems with desired properties, provide an alternative perspective for us to ultimately understand our living world, and promise solutions to some of the most pressing problems in human health.
In the Shirts group, we design and characterize new materials at the nanoscale through the use of theory and computation. Our focuses include drug design through prediction of physical properties and binding affinities and the design of novel biomimetic materials. We are especially interested in the development of computational tools that can fundamentally change molecular design by making searches through chemical and configurations space much more predictive, reliable and efficient.
Proteins are Nature's building block of choice for the construction of ‘molecular machines': stable yet dynamic assemblies with unparalleled abilities in molecular recognition and logic. The King group incorporates these features into the design of functional protein-based nanomaterials with the goal of creating new opportunities for the treatment and prevention of disease. We use computational protein design and a variety of biochemical, biophysical, and structural techniques to produce and characterize our novel materials.
Job Titles:
- Web and Social Media Chair
The Horowitz lab studies citizen science and scientific computer gaming using the biochemistry game Foldit. Our work with Foldit focuses on integrating experimental data into the game, and developing new educational tools and approaches. These efforts improve the speed and accuracy of structural biology investigations, as well as providing hands-on science teaching tools used world-wide. Additionally, we study how nucleic acids impact protein folding and aggregation using strategies ranging from genetics to biophysics.
Job Titles:
- Director
- Workforce Development Chair
The Lindert group engages in computational biophysics research. Research in the lab focuses on the development and application of computational techniques for modeling biological systems of varying sizes. We are particularly active in the field of protein structure prediction using mass spectrometry (covalent labeling, surface induced dissociation, ion mobility) and cryo-EM data. We also study protein dynamics and investigate protein-ligand interactions for drug discovery.
The Schiffner lab combines computational protein design with experimental in vitro high-throughput screening methods to develop "smart" vaccine immunogens. We use technologies such as antibody/antigen interface optimization, epitope grafting, protein resurfacing, T-cell epitope engineering, glycan masking, immunogen multimerization, and protein stabilization and apply them to the rational design of next-gen immunogens against a variety of pathogens, such as Coronaviruses, Hepatitis C Virus and Human Immunodeficiency Virus.