Rotation projects include development of nanobodies for prevention and treatment of mucosal disease (viral and bacteria).
Endowed Chair in Biochemistry and Molecular Biotechnology I
School of Public Health and Health Sciences
Dept of Biochem & Mol Biol And Dept of Chem
Biostatistics And Health Services Research
Additional information about lab rotations within the CPHR program can be found athttp://www.umassmed.edu/cphr/program/rotations.aspx
The project aims to develop computational algorithms and software programs for analyzing high-throughput sequence data such as ChIP-Seq RNA-Seq small RNA sequencing data. PhD required. A strong background in computational biology especially experience with analyzing high-throughput sequencing data is highly desirable. Excellent communication and writing skills and the ability to work with experimental and computational collaborators are essential. To apply please forward CV cover letter and three references to: Zhiping.Weng@umassmed.edu
Please contact Dr. Weng for information on rotations that are available in her lab.
Rotation Projects Rotation projects are available in support of our research. See the research description section of this page.
Rotation projects We apply X-ray crystallography and biochemical methods to understand the mechanisms employed by the ribosome. Potential rotation projects are 1) to understand various aspects of translation via mutagenesis/biochemical assays, 2) to crystallize and work on determining the structures of translation factors and functional ribosome complexes, and 3) to improve computational methods used to determine crystal structures of macromolecules. Feel free to contact the lab for a more detailed discussion.
David J. Freelander Memorial Professor in AIDS Research
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
UMass Chan Medical School Chair in Biomedical Research
A postdoctoral position is available to study in this laboratory. Contact Dr. Rock for additional details.
Potential Rotation Projects <p >Rotations are available in Dr. Rock’s laboratory for graduate students in the GSBS program. The rotation projects will explore various aspects of how the immune system carries out surveillance to detect viral infections and cancers. Among the potential areas of research are: (1) The alarm signals that alert the immune system to potential danger; (2) The initial innate immune and inflammatory response to infection or other dangerous situations; (3) The biology of the sentinel cells (e.g. dendritic cells) that sense danger and report it the adaptive immune system; (4) The mechanisms by which sentinel cells (e.g. dendritic cells) acquire and display antigens to T cells; and, (5) The antigen presentation pathways by which virally infected or cancer cells display a sampling of their expressed gene products to the activated T cells. Specific rotation projects are chosen based on the student’s interests and state/availability of the various projects in the laboratory. The goals of rotations are for the student to gain knowledge in immunology, to learn how to approach experimental problems, to learn new techniques and methods, and to actually generate data that moves our knowledge forward. In addition, the rotation provides the student the opportunity to evaluate the laboratory as a possible place to conduct their thesis research in the future.
Remondi Family Chair in Biomedical Research
POSTDOCTORAL POSITION: RNAI PRECLINICAL DEVELOPMENT Excellent training opportunity for a person considering industrial carrier in drug development Oligonucleotides represent a new class of drugs, which have the promise to become a major class of future therapeutics. There are several classes of oligonucleotides which can efficiently silence genes in various tissues with acceptable level of toxicity. There are also new chemistries being developed to further improve oligonucleotide tissue distribution and cellular uptake. The successful candidate will be a key part of an intra-disciplinary team working with biologists and chemists to develop novel types of therapeutics for treatment of neurological disease, liver disease and orphan indications. The work will include compounds identification, screening, characterization, in vivo efficacy and PK/PD studies, novel assays development etc. In addition exposure and training in nucleic acid pre-clinical development, project management etc will be provided. QUALIFICATIONS: Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and ideally, have research experience in nucleic acid molecular cell biology or pharmacology.
RNAI MEDICINAL CHEMISTRY/ RNA OLIGONUCLEOTIDE CHEMISTRY Develop and characterize novel RNA chemistries to promote efficient oligonucleotide internalization and tissue distribution. Oligonucleotides represent a new class of drugs, which have the promise to become a major class of future therapeutics. There are several chemistries and formulations developed by us and others that effectively support oligo internalization and favorable PK/PD. In most cases in vivo efficacy is limited by (1) poor PK (2) inefficient tissue distribution (3) compound entrapment in biologically inactive intracellular compartments. The objective of future studies will be development of novel chemistries, which promote receptor mediated cellular internalization and/ or endosomal escape. The successful candidate will be responsible for the design and synthesis of novel RNA precursors, optimization of RNA synthesis and conjugation protocols and interface with the biology part of the lab. In addition, exposure to pre-clinical development programs and oligonucleotide manufacturing will be available. QUALIFICATIONS: Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and have previous experience in nucleic acid / oligonucleotide chemistry.
SMALL RNA TRAFFICKING Discover, characterize and adapt mechanisms of small RNA extracellular and intracellular trafficking for development of novel classes of oligonucleotide drugs. A serious limitation in realizing the potential of oligonucleotide based therapies has been the exceedingly inefficient transit of oligonucleotides from outside cells to the intracellular compartments where the biologically relevant activity happens. On the other hand, there are multiple lines of evidence supporting the notion that nature has implemented evolutionarily conserved mechanisms and pathways for efficiently trafficking small RNAs across cellular boundaries. The objective of future studies will be the systematic evaluation of mechanisms of cellular uptake of different classes of oligonucleotides and their comparison to mechanisms of native RNA trafficking using a combination of experimental approaches, including advanced RNA chemistry and high temporal and spatial resolution microscopy in living cells, Mass spectrometry, cell biology and others. The successful candidate will work closely with Victor Ambros and Silvia Corvera labs and the UMASS imaging group and receive training in RNA chemistry, biochemistry, cell biology and pre-clinical development. QUALIFICATIONS:Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and ideally, have research experience in nucleic acid molecular and cell biology
Our laboratory uses a combination of nucleic acid and oligonucleotide chemistry, biochemistry, cell biology, and pharmacology and develops and evaluate novel technologies for development of oligonucleotide therapeutics. A rotation project is available to develop and identify chemically modified self-delivering RNAi compounds for treatment of Huntington and other diseases.
Neil and Margery Blacklow Chair in Infectious Diseases and Immunology
<Long Text /> Potential Rotation Projects Project #1: Probing the structural basis for cooperativity in a dimeric hemoglobin: Scapharca dimeric hemoglobin is an elegantly simple model system for exploring the structural basis for intersubunit communication. Our analysis to date has established a new paradigm for cooperativity in which tightly bound water molecules are used as sensors for ligand state. In this project, the student will first mutate the gene for the native hemoglobin at a residue that is suspected of playing a role in the intersubunit communication. The mutated protein will then be expressed in E. coli and purified and subjected to functional analysis of oxygen binding. Using conditions already established for the native protein, the mutant hemoglobin will then be crystallized and subjected to preliminary x-ray analysis. This project will provide the student with an introduction to two of the most powerful techniques for investigating the structure and function of proteins: site-directed mutagenesis and x-ray crystallography. Additionally, valuable experience in protein purification will be obtained. Project #2: Structural analysis of the polymerization of sickle-cell hemoglobin Sickle cell disease results from the pathological polymerization of deoxygenated hemoglobin S (ß6E->V) within erythrocytes. This polymerization depends upon a complicated interplay of multiple interactions between tetramers. Our high resolution crystal structure of this molecule has elucidated details of some of the important interactions. Several projects are available for rotation students. These include crystallization of sickle-cell hemoglobin in the presence of an inhibitor to identify its binding site, site-directed mutagenesis of hemoglobin S and crystallization of mutants that show altered polymerization characteristics.
Immediate opening! Two postdoctoral positions are available immediately to study cellular andmolecular mechanisms resulting in immunosuppression after alcohol use. Thefocus of this research is the role of monocytes and dendritic cells indecreased antigen-specific T cell activation after alcohol use.Intracellular signalling mechanisms resulting in decreased NF-kBactivation and inflammatory cytokine induction after acute alcoholconsumption are being investigated. Please contact Dr. Szabo for details.
Potential Rotation Projects Contact Dr. Sullivan for more project details.
Gretchen Stone Cook Chair in Biomedical Sciences
A postdoctoral position is available to study in this laboratory. Contact Dr. Zamore for additional details
Potential Rotation Projects Our laboratory uses a combination of biochemistry, cell biology, and genetics to dissect the RNAi pathway. A rotation project is available to explore the mechanisms that underlie the RNAi phenomenon or the biological pathways in which RNAi enzymes participate in flies, mice and humans.
Postdoctoral positions are available to study the relationship(s) between the Rb/E2F proliferation pathway and p53-dependent apoptosis. Areas of investigation include understanding why E2F1 is unique among the E2F family in its strong apoptosis signaling ability and determining the pathways that lead from E2F1 activation to cell death. Fellows will be associated with a highly motivated and interactive group of researchers studying aspects of cell cycle, apoptosis signaling and cancer using cell culture, virology and animal models. If interested, please contact: Timothy Kowalik Department of Molecular Genetics and Microbiology University of Massachusetts Medical School 55 Lake Avenue North Worcester, MA 01655 The University of Massachusetts Medical School is an Affirmative Action / Equal Opportunity Employer.
Rotation Projects Identify the region on E2F1 responsible for p53-mediated apoptosis. We know that a transcriptionally functional E2F1 is required for apoptosis signaling. We also know that E2F2 does not induce apoptosis in our system. Therefore, domains on E2F1 and E2F2 will be swapped to determine which E2F1 domain is responsible for apoptosis signaling. Role of nuclear kinases in E2F1 mediated apoptosis. Our recent efforts have revealed that E2F1 expression leads to the phosphorylation of p53 and this modification correlates with apoptosis. There are several candidate kinases that need to be analyzed for their contribution to p53 phosphorylation. A dominant negative approach will be used in this project to identify which kinase(s) contribute to the E2F1 signal to p53. Role of CMV IE proteins in proliferation. We have found that both IE1 and IE2 target different Rb family members. IE2 binds to Rb and IE1 interacts with p107. We now know that IE2 is a strong inducer of S phase but IE1 can only significantly modulate proliferation in cells lacking p53. We are interested in knowing why p53 can prevent IE1 from inducing S phase. Mechanism of p53 accumulation by CMV. It has recently been shown that CMV infection results in an accumulation of p53. We have recently found that IE1 expression also leads to p53 accumulation. We wish to determine the steps leading to p53 accumulation and the consequences of this event.
Focus: Cellular and organismal studies of viral infections
Arthur F. and Helen P. Koskinas Professor in Biochemistry and Molecular Biotechnology
A postdoctoral position is available to study in this laboratory. Contact Dr. Lambright for additional details.
Lab Rotations <p >Our lab takes an interdisciplinary approach to the study of fundamental problems in cell biology, signal transduction and membrane trafficking. Rotation projects are available in any of the areas of interest to the lab. Projects are tailored to the individual interests of the students and often involve a combination of molecular, biochemical, biophysical, structural and/or cell based analyses to investigate signaling and trafficking mechanisms. <p >
UMass Memorial Health Care Chair in Biomedical Research
Potential Rotation Projects: Contact Dr. Luzuriaga for project details.
A postdoctoral position is available to study in this laboratory. Contact Dr. Craig for additional details.
Potential Rotation Projects Project #1: Lipid-Layer Protein Crystallization for Electron Microscopy.While individual protein molecules can be readily visualized by EM, structural information is greatly enhanced if the molecules can by crystallized into 2-dimensional ordered arrays. Methods for achieving this are well established, making use of lipid monolayers at an air-water interface. Follow literature methods to crystallize "standard" proteins using the lipid-layer method. Observe results by electron microscopy following negative staining. If time permits, carry out preliminary image processing of micrographs and/or crystallization of unknown proteins. Techniques to be learned: lipid layer crystallization methods; grid preparation; use of electron microscope; image processing.
Potential Rotation Projects Several rotation projects are available in structural biology of immune receptors, antigen presentation pathways, T-cell activation, and development of novel T-cell detection reagents. Please see Prof. Stern for details.
A postdoctoral position is available to study in this laboratory. Contact Dr. Gottlinger for additional details.
Potential Rotation Projects 1.The identification of novel binding partners for cellular proteins required for HIV-1 budding using a double tag immunoaffinity purification approach. 2.The characterization of mutant ESCRT-III components that block HIV-1 budding with regard to subcellular localization and their ability to interact with certain phosphoinositol lipids and with other proteins involved in late endosomal sorting. 3.The mapping of binding sites for cellular proteins that we have identified as specific components of HIV-1 using GST pulldown, yeast two-hybrid, and co-immunoprecipitation approaches. 4.The generation and functional characterization of mutant viral Gag proteins that fail to interact with specific cellular partners.
Potential Rotation Projects <p >Our laboratory combines genetic and biochemical approaches to investigate the molecular underpinnings of adaptation. Potential rotation projects are available in two general (and partially overlapping) areas: exploring fitness landscapes through systematic approaches and investigating the molecular mechanism of the Hsp90 chaperone in signal transduction. Please contact the lab to discuss specific rotation projects in more detail.
Population and Quantitative Health Sciences
Focus: The Munro laboratory develops and applies quantitative biophysical approaches to visualize virus replication, and probe the functions of the proteins and RNAs involved.
Focus: Viral entry, antibodies & vaccines, single molecule techniques
Biochemistry and Molecular Biotechnology
Jack M. Wilson Chair in Biomedical Research
Joseph D. Early Chair in Biomedical Research