The Antoniewicz lab for Metabolic Engineering and Systems Biology works on a wide range of topics in modern life sciences including Biofuels and Diabetes, where we apply techniques such as Metabolic Flux Analysis, Stable-isotope Labeling Experiments, e.g. 13C, 2H, 18O, and Tandem Mass Spectrometry to study cellular systems. The primary goal of our research efforts is to provide a comprehensive understanding of the function and regulation of complex biological processes that emerge through the interaction of genes, proteins, and metabolites at multiple metabolic and genetic regulatory levels. To achieve this, we develop novel experimental and computational tools to quantify cellular physiology and apply genome-wide models of cellular interactions to interpret the large sets of biological data generated from these technologies.
Our interests range from looking at model microbial systems, i.e. Saccharomyces cerevisiae and Escherichia coli, to investigations of mammalian cells such as hepatocytes, adipocytes and myocytes. Beyond large-scale identification of interactions and transcriptional control of network operations in isolated cells, we develop technologies for studying disease phenotypes at the whole organism level. Our results find applications in many areas including industrial biotechnology, e.g. metabolic engineering of microbial cells for the production of biofuels and biochemicals, and medicine, in particular, investigations of human metabolic disorders such as Type-2 Diabetes.
Structural Enzymology. We are focusing on a group of human HDL and LDL associated
enzymes that have direct links to atherosclerosis. Also, one of the
systems currently under study is also a promising catalyst for the
detoxification of organophosphate neurotoxins. We use a combination of
protein expression, site-directed mutagenesis, kinetics, homology modeling
and x-ray crystallography to understand the relationship between structure
and function for these systems, with goal of either inhibiting detrimental
activities or designing more specific catalytic activities.
Probing receptor interactions on neurons and other cell surfaces
directly with the AFM; Development of micropatterned biomaterials and
controlled surfaces for cell-surface interactions; Molecule corrals and
nanostructures for molecular control; XPS, TOF-SIMS, AFM and other
The extracellular matrix plays key roles in developing tissues,
maintenance of tissue function and pathological states such as cancer. Our
lab is particularly interested in the role that proteoglycans, mucins and
their corresponding binding proteins play in mammalian reproduction and
cartilage function. Transgenic mouse models as well as a variety of
biochemical and molecular biological approaches are used to study these
Bone metastasis is a debilitating complication of advanced prostate cancer. My research focuses on the role cell adhesion plays in prostate cancer preferential metastasis to bone. Presently, we are seeking to identify the cell adhesion molecules (CAMs) involved and how they are regulated by components of the bone microenvironment. In addition, we are interested in the contribution of prostate cancer adhesion to bone matrix components to chemosensitivity and cell survival.
We are interested in candidate or novel genes that play a role in spermatogenesis, epididymal sperm maturation, and fertilization. A major focus is the "germ-cell specific" hyaluronidases of which the Sperm Adhesion Molecule 1 (SPAM1) is the best characterized. Molecular genetic approaches, including gene targeting and transgenesis, are being used to gain insights into the mechanisms leading to sperm dysfunction and male infertility associated with the over-expression of this gene. We are also studying the post-transcriptional control of murine Spam1 as a model of spermatid-expressed genes.
Our group is interested in the molecular control of vertebrate eye development and blinding eye disease. Most of our investigations study this process during in the ocular lens, a simple epithelium comprised of two general cell types, lens epithelial cells that maintain the ability to proliferate, and terminally differentiated lens fiber cells which derive from the epithelium. The lens is a particularly good tissue for the study of cellular differentiation since the two cell types are spatially separate and morphologically dissimilar. Further, since abnormalities in lens development do not affect the survival of laboratory animals, it is possible to genetically manipulate pathways controlling lens formation without fear of lethality.
The primary focus of my research is the study of signal transduction mechanisms involved in the response of musculoskeletal cells to mechanical and hormonal stimulation, concentrating on Ca2+ signaling. This line of research can be divided into three major themes; 1) Mechanotransduction: defining the mechanisms involved in the initial response of musculoskeletal cells to mechanical stimulation, 2) Cytomechanics: examining the mechanical parameters of the cells important in adaptation and return to responsiveness of the cells following chronic mechanical loading and 3) Hormonal Synergy: discerning the mechanisms behind the interaction of calciotropic hormones and mechanical stimulation.
Role of calcitropic hormones in the bone remodeling process, primarily
on bone-forming osteoblasts. Interplay between hormonal and mechanical
factors in bone health and disease. Role of bone matrix in the progression
of cancer following metastasis from primary sites, such as prostate, to
bone. Heparan sulfate proteoglycans in bone and cartilage.
Our research interests lie at the intersection of three major themes: The structure, rheology and phase behavior of complex fluids, such as colloidal and biopolymer systems; Cellular mechanics and movement, including cell rheology and the behavior of cytoskeletal biopolymers and structures; and Interfacial phenomena as they relate to understanding and controlling colloidal interactions and stability. By applying new tools based on single-polymer visualization, microrheology and optical trapping, we have an unprecedented ability to guide the assembly, deform structures, measure stress and study dynamics at a microscopic scale to better understand and control material and biological properties and responses.
of Plant and Soil Sciences and College of Marine Studies
Regulation and Function of RNA: Combining biochemical, molecular
genetic, and genomic approaches. Messenger RNA is of critical importance to cells as the key
intermediate in gene expression and its abundance usually dictates the
amount of protein produced from a gene. Rates of synthesis and degradation
both contribute to the abundance of mRNAs, although less is known about
how the latter (mRNA stability) is controlled. Interestingly, some genes
produce RNA rather than protein as their final product and investigators
are just beginning to unravel the roles of such "noncoding RNAs." The
Green lab addresses fundamental questions about the control of mRNA
stability, RNA-degrading enzymes, and the functional genomics of noncoding
RNAs, mainly in the model plant Arabidopsis, but also in yeast and marine
Materials Science and
The overall goal of our research is to design and synthesize biomimetic materials with controlled architectures and functionalities for biomedical applications. The first area aims at engineering artificial extracellular matrices (ECM) that are not only reconfigurable and adaptable, but also exhibit desired mechanical properties that are conductive to tissue growth. The second research area is soft tissue engineering, with an emphasis on vocal fold tissue regeneration. We are evaluating vocal fold biomechanics at both cellular and tissue levels. We are also studying vocal fold ultrastructure from molecular level up to macroscopic scale. This knowledge will be applied to the design of functional vocal fold substitute materials.
Protein characterization by mass spectrometry. Multidimensional peptide and protein separations coupled to mass
spectrometry; high throughput proteomics using two dimensional gel
electrophoresis and mass spectrometry; protein identification, structure
elucidation and de novo sequencing by mass spectrometry; matrix-assisted
laser desorption ionization, electrospray ionization, and tandem mass
Materials Science and Engineering
Protein based materials; de novo design of artificial protein polymers;
protein-saccharide self-assembling hydrogels; drug delivery matrices;
biopolymer processing; light-emitting biopolymers. Protein engineering methods provide a powerful synthetic method for
producing polymeric materials whose structure and composition are
precisely controlled. Our group utilizes a combination of protein
engineering and chemical strategies to design and synthesize novel
macromolecules for applications in biology and materials science.
Potential applications include toxin neutralization, mediation of
chemotactic events, drug delivery, growth factor delivery for biomaterials
applications, light-emitting diodes, and self-assembled
The research focus of this laboratory, centers on the development of novel DNA or RNA molecules that can direct genetic changes in the chromosomes of mammalian cells and animal models. We use biochemical and genetic tools to study the mechanism by which these changes occur and how the cell regulation this process. Presently, the vector of choice is a single-stranded DNA oligonucleotide that mediates the correction of single base mutations using the endogenous DNA repair and recombination activities. The repair of single base mutations by these oligonucleotides is being tested as a gene therapy approach for several inherited disorders.
Plant & Soil Science
Intercellular communication is fundamental to every living organism for their survival. Both animals and plants have evolved unique systems that provide cytoplasmic passageways for ions, metabolites and small signaling molecules between cells. In plants, the cytoplasmic channels are called plasmodesmata. Fascinatingly, plasmodesmata have the additional capacity to mediate trafficking of macromolecules such as proteins and various forms of RNA. We are exploring the molecular mechanisms and players involved in macromolecular trafficking through plasmodesmata to better understand the role of plasmodesmata in this event and in plant growth and development.
Applied protein biophysics; fundamentals of separations processes;
protein interactions with surfaces and in solution; protein thermodynamic
properties and phase behavior; crystallization and precipitation;
fundamentals of protein chromatography.
Kelvin H. Lee
With the right tools, one can identify the genetic basis for many different phenotypes or disease states. Our research laboratory is focused on the development of next generation tools for protein expression profiling and the use of existing tools applied to specific problems in biomolecular engineering and medicine. Our current areas of focus include: 1) the use of proteomics in support of a passive immunization clinical trial for the treatment of Alzheimer's disease; 2) the study of enhanced heterologous protein secretion in bacterial and mammalian cells including a detailed understanding of protein translation; and 3) the development of nanoscale materials and technologies for protein separation. We rely heavily on computational methods as well as biological mass spectrometry and we actively pursue both gel-based as well as shotgun-based proteomics approaches.
We are interested in developing computational tools-particularly by incorporating the domain specific knowledge - to solve biological problems. Our current research is focused on detecting the sequential and structural features of proteins, and using them to identify and understand relationships among proteins. Our work includes graph-theoretic clustering algorithms to tackle multi domain proteins; support vector machines combined with pair wise similarity and phylogenetic information to detect more remote homology; and hidden Markov models to predict transmembrane protein topology.
Plant & Soil Science
We work in two areas of plant molecular biology. We use a novel technology called 'massively parallel signature sequencing' for genome-wide transcriptional analysis of mRNA and small RNAs in Arabidopsis and rice. This requires a number of bioinformatics tools and approaches for handling and analyzing the data. We have described novel patterns and types of gene expression, and we are experimentally validating these results. The second research project is characterizing the function and evolution of two families of Arabidopsis genes. Sequence similarities, inferences from animal innate immune signaling systems, and gene clusters suggest that these two families of genes function in plant disease resistance signaling. These plant proteins may be components of an ancient host defense system that evolved prior to the divergence of plants and animals.
Our research interest is to understand the molecular mechanism of
signal transduction involved in cardiovascular disease and cancer.
Cell-cell interactions and cell-extracellular matrix interactions play key
roles in these diseases. One of our research interests is studying the
molecular mechanisms involved in platelet aggregation (initiation of
thrombus). Understanding the signaling events involved in this process may
help develop remedies that target myocardial infarction and stroke.
Another area of interest is to elucidate the role of cell adhesion
molecules belonging to the immunoglobulin superfamily in tumor-induced
angiogenesis. Our studies routinely involve cell and molecular biological techniques as well
as knock-out animal models to better understand the molecular mechanisms
involved in pathological angiogenesis.
Our goals are to develop multidimensional fluorescence techniques and
multivariate data analysis methods to monitor dynamic interactions in
microheterogeneous biological media, such as model membranes and membrane
bound or associated proteins using multi-state, microenvironment-sensitive
probes. We are combining a variety of fluorescence measurements, including
spectral, photokinetic, anisotropy and energy transfer measurements, into
multidimensional methods for simultaneous monitoring of multiple
excited-state interactions between probe molecules and biological systems.
Currently, we are using these methods to investigate temperature-induced changes in mixed lipid
aggregates (bicelles) and chemically induced changes in
Our research efforts are organized around the general theme of first understanding the dynamic behavior of complex systems through mathematical modeling and analysis, and then exploiting this understanding for novel designs and improved operation. The particular complex systems of interest range from polymer reactors, particulate processes and extruders, to biological systems on the cellular, tissue, and organ levels. When sufficient fundamental knowledge is available, we develop and employ dynamic “mechanistic” models; when more data is available than fundamental knowledge, we apply probability theory and statistics for efficient data acquisition and “empirical” model development.
Materials Science and
We are exploring the rules underlying the molecular design and
self-assembly of unique biopolymeric and bioorganic-inorganic hybrid
materials. Biomaterials are being constructed via the design and
self-assembly of polypeptide molecules taking advantage of the large tool
box of inter/intramolecular interactions and molecular conformations
available in peptides. Ultimately, secondary structure phase transitions
and specific interactions sensitive to their environment will produce
materials whose structure, and consequent function, will be sensitive to
desired environmental cues. A variety of microscopy (transmission and
scanning electron, optical, laser scanning confocal and atomic
force/surface probe) and scattering (small- and wide-angle x-ray and
neutron) techniques are used to elucidate bulk, solution, and thin film
structures. In addition, the cell and tissue level biological properties
(e.g. biocompatibility/cytotoxicity) of materials are assayed in a new
cell culturing lab located in the Delaware Biotechnology
Materials Science and
The Rabolt group investigates the assembly of engineered proteins into
fibers to create novel biomimetic materials. The group is expert at
development of vibrational spectroscopic methods for "real time" probing
of the evolution of microstructure in commercially melt spun and
electrospun fibers. They collaborate with Bruce Chase (DuPont) and Richard
Ikeda (Adjunct Professor - MSE and DuPont - Retired)] to study
commercially important systems.
Research in Dr. Roberts’ laboratory is centered on bio-physical chemistry and modeling of protein degradation; both in solution and in amorphous solids typical of commercial protein products. There is particular emphasis on understanding protein aggregation and other degradation routes from the perspective of interactions between non-native proteins, solvent-mediated and solute-mediated forces, the interplay between chemical and physical degradation routes, and the influence of conformational state on reactivity.
Our laboratory is taking two approaches to increase our understanding and ability to control molecular interactions and cellular functions: 1) Examining proteins in isolation to identify important interactions in folding and assembly in an effort to control those interactions to optimize this process. 2) Identifying interactions in the cell that control protein expression, and altering the interactions to maximize production of functional proteins. Our research is focused on expression of membrane proteins (G-protein coupled receptors), characterization of the stress response in yeast, and characterization and reversal of misfolded proteins (antibodies and membrane proteins).
Our research entails the de novo design of functional peptides and
proteins. Ongoing efforts are highly interdisciplinary and span
historically disparate disciplines of science such as materials science,
inorganic and organic chemistries, chemical synthesis and biophysics. As
chemists, we are not limited to the naturally occurring amino acids in our
designs and we often incorporate non-natural residues, which we design and
synthesize, into peptides and proteins to impart unique structural and
functional properties. General design strategies for the preparation of
peptide-based antibiotics, recognition motifs for protein folding
specificity, peptide and organoarsenical-based probes, as well as
bio-inspired materials are actively being pursued in the Schneider
Posttranslational modification of extracellular molecules has recently
been shown to play a crucial role in the temporal and spatial regulation
of signal transmission by altering extracellular receptor-ligand
interactions. The objective of my research is to use Drosophila
melanogaster as a model system to study the function of posttranslational
changes that influence developmentally critical signaling
Our research focuses on the formation and function of a novel membrane
in nitrogen-fixing root nodules, the symbiosome membrane. This membrane is
derived from the plant plasma membrane and becomes specialized during root
nodule development. Our goal is to understand how this unique membrane is
formed and how its protein content influences nodule function. The results
from this work will help us understand interactions of plants with soil
microbes, development of plant tissues, and targeting of proteins within
plant cells. Our group utilizes a wide spectrum of methods to study this fascinating
membrane. These include biochemistry, molecular biology, cell biology,
biotechnology, and classic botany.
My research is focused around the normal development of the mouse prostate and the development and progression of prostate cancer. Voltage-sensitive sodium channels (VSSCs) are transmembrane ion channels that open in response to membrane depolarization. My lab has been screening novel inhibitors of voltage-gated sodium channels (VGSC) for anti-tumor effects. Several lead compounds are now in preclinical animal testing The promising inhibitory results have shifted our attention on the biology of VGSCs in the metastatic phenotype. This includes cell motility and the role of VSSC in neuroendocrine differentiation of the prostate.
Our laboratory is interested in the structure and function of the simian virus 40 tumor antigen (T antigen) and of cellular proteins that interact with it in virus infected and transformed cells. T antigen is a multifunctional phosphoprotein synthesized early in SV40 infection. It is required for virus DNA replication and for the regulation of viral gene expression in infected cells. The protein is also required for the induction and maintenance of malignant transformation of nonpermissive cells. By using a multifaceted biochemical and genetic approach, we are investigating the fine structure and activity of various functional domains of T antigen and correlating this information to the biology of SV40. Our present effort is focused primarily on T antigen's role in the initiation and elongation phases of SV40 DNA replication.
Millicent O. Sullivan
The goal of our research is to design improved biomolecular strategies for therapeutic payload delivery to pre-determined cellular/sub-cellular locations. While a variety of drug and DNA packaging methods exist, what is missing are systematic studies of the processing and fate of these packages by and within cells, and a strong mechanistic link between materials design and the expected interactions within the extra- and intracellular environments. Materials evolution could render a delivered therapy ineffective, or conversely, might enhance drug transport or utilization. The emphases of our program: 1) To promote improved understanding of how the chemical and physical interactions between nanomaterials and the intracellular environment affect material stability, structure, and fate. We employ readily manipulable nanomaterial systems to systematically investigate how different material properties are affected by the environment. 2) To enable rational/predictive design of drug delivery nanomaterials by applying our understanding of the subcellular environment to pre-programming desirable material responses. These responsive biomaterials are applied to solving critical problems in drug/gene delivery.
Professor Bernhardt's research interests center on visual rhetoric,
computers and writing, workplace training and development, and the
teaching of scientific and technical communication. As consultant to the
pharmaceutical industry, he helps such companies as Pfizer,
Schering-Plough, and AstraZeneca design large documentation sets, use
global teams and technologies, deliver training programs, and improve
written communication as a part of new drug development and
I am interested in intergroup relations and in particular, how prejudice, discrimination and intergroup conflict can be reduced. My current research explores the possibility that inducing the members of two groups to conceive of themselves as a single, more inclusive group or as subgroups within the same inclusive group structure (i.e., a dual identity), can harness cognitive and motivational processes that encourage more harmonious intergroup relations.
Dr. Sawyer investigates the effects of individual characteristics and
group processes on creativity and organizational innovation. His current
research includes a qualitative and quantitative meta-analysis of
creativity research and development of procedures for enhancing R&D
productivity. Additionally he is currently investigating information
sharing and integration in cross-functional, racially diverse decision
making groups, and the impact of virtual teamwork on knowledge transfer
and problem solving. Past empirical research on teams included the effects
of social uncertainty on group member's allocation of time and effort to
group tasks. Other published work includes studies of the effects of
ambiguity and uncertainty on individual judgment processes and their
impact on individual behavior, resource allocation decisions, work
behaviors, work performance and attitudes.