The Aroian Group is actively recruiting graduate students to: 1. use microbiology and genetics to develop new methods for delivery of protein therapies (anthelmintics) to the GI tract 2. discovery and mechanism of action studies of new anthelmintics to control soil-transmitted helminths 3. study how vertebrate hosts and their immune system interact with intestinal nematodes, with the particular goal of controlling autoimmune disease 4. study innate immune mechanisms that protect animals against pore-forming toxin attack
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
Blais University Chair in Molecular Medicine
Potential Rotation Projects: There are numerous potential rotation project available in the Mello lab: Projects include: Investigation of RNAi and related mechanisms, including Piwi Argonaute pathways and their affects on fertility and epigenetic inheritance; Investigation of germline determination and cell-fate specification during embryogenesis; the exploration of CRISPR mediated genome editing tools for C. elegans and other organisms; and finally the use of CRISPR to generate C. elegans models for human genetic disease.
Rotation Projects Rotation projects are available to address the following questions: How does the lack of structure in the C-terminal zinc finger of TTP affect the activity of the protein in the cell? In humans, there are three members in the TTP protein family: TTP, TIS11b and TIS11d. Structural studies performed by us and others have shown that while the TZF domain of TTP is partially unstructured in the free state and folds upon binding RNA, those of TIS11d and TIS11b are always folded. We have shown that the degree of structure of the TZF domain affects the activity of the protein in cells and indicates that the protein can modulate its activity through its dynamics. We want to determine whether structural disorder is directly linked to cellular stability or protein localization How do mutations in the RNA-binding domain of TIS11d cause cancer? Several point mutation in TTP and TIS11d have been linked to cancer. In particular, point mutations in the RNA-binding domain of TIS11d are found in leukemia patients. We are currently working on the characterization of the structure, dynamics and biological activity of these mutant proteins to understand their role in the pathogenesis of cancer. How does HuR regulate the stability of its target mRNA? HuR is another protein that, like TTP, binds to AU-rich elements (ARE) in mRNAs and regulate their stability. The detailed mechanisms that determine how HuR regulates transcripts stability are poorly understood. We are investigating how binding or HuR to the 3’UTR of an mRNA leads to its stabilization.
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.
Governor Paul Cellucci Chair in Neuroscience Research
Project 1: Dervelop RNA-based therapies for frontotemporal dementia (FTD) and related disroders. Project 2: Study pathogenic mechanisms of FTD and related disorders in mouse models.
Our lab uses a combination of molecular, cellular, genetic, and behavioral approaches to further dissect the pathogenic mechanisms of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis with a focus on mutant CHMP2B, progranulin and C9ORF72. We will identify common underlying pathways as potential targets for therapeutic interventions.
Pleas e-mail Daniel Caffrey if you are interested in rotations.
David J. Freelander Memorial Professor in AIDS Research
Dr. Strambio-De-Castillia (ORCID: https://orcid.org/0000-0002-1069-1816) is an internationally recognized cell biologist and imaging scientist who specializes in developing easy-to-use and openly accessible strategies for image data management and sharing to promote scientific discovery in health and disease.
If you are interesting in applying computational methods to biological problems please contact me. Potential projects in my lab are Modeling of transcription factor gene expression control in innate immune cells Evolutionary analysis of gene transcription factor networks in mammals Epigenetics inheritance in mice: From male sperm to phenotypic effect in grandchildren Application of genome and exome sequencing to newborn screening Development of computational methods for analysis of RNA-protein interactions
Dr. King is a computational biologist with research interests in algorithm development and the analysis of high-throughput datasets. His current research projects involve facioscapulohumeral muscular dystrophy (FSHD), amyotrophic lateral sclerosis (ALS), and other disorders.
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.
Arthur F. and Helen P. Koskinas Professor in Biochemistry and Molecular Biotechnology
Postdoctoral Fellow Applications are being accepted for one position. A position is available to develop Cys2His2 zinc finger proteins (ZFPs) for the treatment of monogenic disorders. This project will focus on the creation of ZFPs with novel DNA-binding specificity to recognize sequence elements within genomic loci of therapeutic interest. In collaboration with other laboratories, we will evaluate the activity of these ZFP-based gene therapy reagents in vitro and in vivo in relevant disease models. Applicants will also have the opportunity to learn to apply Cas9 and Cas12a editing systems in vivo.
Potential Rotation Projects Improving the Precision of CRISPR/Cas9 nucleases for gene therapy applications: We are working to improve the precision of the CRISPR/Cas9 system to generate nucleases that will cleave at only a single site in the genome. These engineering efforts focus on increasing the DNA-editing precision of Cas9 and using protein engineering to introduce new properties into the nuclease. Much of this work is now transitioning to the use of Cas9 (and Cas12a) protein-RNA complexes. These modified nucleases will then be applied to patient derived cell-culture systems for the targeted repair or inactivation of disease-causing alleles. With the eventual goal of creating therapeutics for Sickle Cell Disease, beta-Thalassemia, HIV, Limb Girdle Muscular Dystrophy, Hermansky Pudlak Syndrome and other monogenic disorders. ex vivo genome editing in CD34+ HSPCs: We are developing improved Cas9 proteins for delivery ex vivo into CD34+ HSPCs for therapeutic application to sickle cell disease and beta-thalassemia. The goal is to modify the hematopoietic stem cells of a patient to complement the loss of function of the beta-globin gene and then return these cells to the patient through an autologous transplant. Development of Cys2His2 Zinc fingers proteins (ZFPs) as targeted therapeutics: We are developing artificial ZFPs for the regulation of target genes to change their gene expression profiles for therapeutic applications.
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 >
Potential Rotation Projects Rotation projects in my laboratory will involve questions of how cilia are assembled and the function these organelles play in mammals. Projects vary depending on ongoing work in the laboratory and interests of the rotation student. Rotations in my laboratory can give students exposure to a range of techniques from mouse breeding and histological analysis of mouse tissues to mammalian cell culture and other cell biological techniques.
Rotation Project Background
In yeast cells, protein translocation across the endoplasmic reticulum can occur by cotranslational or posttranslational pathways. The objective of this project is to develop a rapid method to inactivate the posttranslational pathway in vivo in yeast cells by appending the CMV-ribosome stalling sequence to the C-terminus of a typical posttranslational translocation substrate (carboxypeptidase Y). Complexes between the posttranslational translocation channel (SEC complex) and the stalled ribosomes will be purified for structural and functional analysis.
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.
Joseph J. Byrne Chair in Biomedical Research
? Rotation Projects Multiple rotation projects are available in several areas related to long-range gene regulation and higher order chromosome organization. Projects include thorough analyses of the biochemical mechanisms of long-range gene regulation of specific disease-related genes, as well as large-scale analyses of chromosome organization using high-throughput genomics technologies (5C and Hi-C). The lab employs a wide range of experimental approaches, including cell culture, protein biochemistry, microscopy, genomics as well computational approaches such as bioinformatics and modeling. Specific rotation projects are determined dependent on the interest of the student.
Rotation Projects <p >We have identified a number of bacterial pathways that are required for bacterial viability or virulence. We are particularly interested in: Phosphosignaling systems that regulate cell wall synthesis Metabolic regulatory mechanisms that trigger the “dormancy” response observed during infection. <p >A variety of genetic, biochemical, and informatic methods will be used to define the functions of these genes and the role played by each during infection. <p >
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.
Richard M. Haidack Professor in Medicine
Dr. Almeida focuses on uncovering the molecular mechanisms underlying frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD). Her research leverages patient-derived induced pluripotent stem cell (iPSC) lines to create neuronal models that closely mimic disease conditions.
Dr. John Meyers Professor in Primary Care Medicine
Population and Quantitative Health Sciences
Biochemistry and Molecular Biotechnology
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