Emmanuel College

U.S. DEPARTMENT OF EDUCATIONCARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND - IHES

U.S. DEPARTMENT OF EDUCATION CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND - IHES

EMERGENCY MANAGEMENT FOR HIGHER EDUCATION

BRC-BIO: ANALYZING THE ROLE OF DROSOPHILA VARIANT POLYCOMB REPRESSIVE COMPLEXES IN DEVELOPMENTAL GENE TRANSCRIPTION -MULTICELLULAR ORGANISMS ARE COMPOSED OF INDIVIDUAL CELLS THAT FUNCTION DISTINCTLY, DUE TO THE REGULATION OF GENE EXPRESSION DURING DEVELOPMENT. DEVELOPMENTAL GENE REGULATION IS LARGELY MADE POSSIBLE BY MANY PROTEIN COMPLEXES THAT TURN GENES ON OR OFF AT APPROPRIATE DEVELOPMENTAL WINDOWS. AN IMPORTANT EXAMPLE IS THE POLYCOMB REPRESSIVE COMPLEX, WHICH TURNS OFF A SPECIFIC SET OF DEVELOPMENTAL GENES. HOW THIS COMPLEX SELECTS THE CORRECT GENES TO SILENCE DURING EARLY DEVELOPMENT IS STILL UNKNOWN. THIS PROJECT WILL UTILIZE THE FRUIT FLY AS MODEL ORGANISM TO STUDY THE ROLE OF THIS SILENCING COMPLEX IN ORCHESTRATING DEVELOPMENTAL GENE EXPRESSION. DISCOVERING THE MECHANISM BY WHICH POLYCOMB REPRESSIVE COMPLEXES SILENCE GENES IN THE FRUIT FLY WILL INFORM OUR UNDERSTANDING OF DEVELOPMENT IN MAMMALS. ANOTHER SIGNIFICANT GOAL OF THIS PROJECT IS TO INCREASE THE PARTICIPATION OF PERSONS TRADITIONALLY EXCLUDED BECAUSE OF THEIR ETHNICITY OR RACE (PEERS) IN UNDERGRADUATE RESEARCH EXPERIENCES AT EMMANUEL COLLEGE. STUDENT RESEARCHERS WILL USE GENETIC, MOLECULAR, AND BIOCHEMICAL TECHNIQUES TO ADDRESS THE AIMS OF THIS PROJECT. COLLABORATIONS WITH RESEARCHERS FROM HARVARD MEDICAL SCHOOL AND BRANDEIS UNIVERSITY WILL FACILITATE ENGAGEMENT OF PEER UNDERGRADUATE STUDENTS WITH THE BROADER SCIENTIFIC COMMUNITY. THE GOAL IS TO INSPIRE LARGER NUMBERS OF PEER STUDENTS TO PURSUE CAREERS IN STEM. MULTICELLULAR DEVELOPMENT IS GOVERNED BY THE DEPLOYMENT OF CELL-TYPE SPECIFIC TRANSCRIPTIONAL PROGRAMMING, IN WHICH A SINGLE GENOME IS UTILIZED DISTINCTLY OVER TIME AND SPACE AS CELLS MULTIPLY AND SPECIALIZE. THIS PHENOMENON IS ACHIEVED BY THE PRECISE COORDINATION OF GENE EXPRESSION THAT INITIATES THE DIFFERENTIATION OF THE DIFFERENT CELL TYPES OF AN ORGANISM. CHROMATIN REGULATORY FACTORS HAVE BEEN FOUND TO BE ESSENTIAL FOR REGULATION OF DEVELOPMENTAL TRANSCRIPTIONAL PROGRAMMING HOWEVER THE MECHANISM BEHIND HOW THESE FACTORS COORDINATE GENE EXPRESSION DURING EMBRYONIC DEVELOPMENT REMAINS UNCLEAR. ONE HIGHLY CONSERVED CHROMATIN REGULATORY SYSTEM THAT PLAYS A CENTRAL ROLE IN DEVELOPMENTAL PATTERNING AND CELL DIFFERENTIATION INCLUDES THE POLYCOMB GROUP (PCG) PROTEINS. THESE PROTEINS ARE TYPICALLY FOUND IN TWO DISTINCT TYPES OF POLYCOMB REPRESSIVE COMPLEXES (PRCS): PRC1 AND PRC2. THE PI'S LAB RECENTLY IDENTIFIED VARIANT PRC1 (VPRC1) COMPLEXES IN DROSOPHILA THAT HAVE STRONG MODULAR CONSERVATION WITH MAMMALIAN COMPLEXES, SUGGESTING AN ANCIENT FUNCTIONAL DIVERSITY. THE GOAL OF THIS WORK IS TO UNDERSTAND THE ROLE OF VPRC1 COMPLEXES IN COORDINATING THE CELL-TYPE SPECIFIC TRANSCRIPTION CRITICAL FOR NORMAL DEVELOPMENT. IN THIS PROJECT, UNDERGRADUATE STUDENT SCIENTISTS WILL FUNCTIONALLY CHARACTERIZE ONE OF THE VPRC1 COMPLEXES USING A VARIETY OF METHODS, INCLUDING CROSSLINKING, TANDEM AFFINITY PURIFICATION, AND INTEGRATED ANALYSIS OF PROTEIN PARTNERS AND DNA BINDING SITES, IN PARALLEL WITH FUNCTIONAL GENETIC APPROACHES TO DISSECT THE CHANGES IN PROTEIN COMPLEXES DURING NORMAL DEVELOPMENT IN DROSOPHILA. SUCCESSFUL COMPLETION OF THIS PROPOSAL WILL PROVIDE MECHANISTIC DETAILS FOR FUNCTION OF A VARIANT PRC1 COMPLEX IN DEVELOPMENTAL GENE REGULATION. RESULTING INSIGHTS WILL PROVE USEFUL FOR FUTURE ANALYSES IN MAMMALIAN CELLS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

RUI: CHARACTERIZING DNA TARGET SEARCH USING SINGLE MOLECULE METHODS

RUI: EARLY ENDINGS - CHARACTERIZING THE ROLE OF HRP1 IN RNA POLYMERASE II TRANSCRIPTION ATTENUATION -LIFE DEPENDS ON INFORMATION STORED IN DNA, WHICH IS EXPRESSED INTO RNA AND PROTEINS THAT PERFORM CELLULAR FUNCTIONS. AN INITIAL STEP OF GENE EXPRESSION IS TRANSCRIPTION, WHERE A MOLECULAR MACHINE CALLED RNA POLYMERASE READS DNA TO SYNTHESIZE RNA. AS RNA POLYMERASE MOVES ALONG DNA, IT CAN BE INTERRUPTED BY REGULATORY STOP SIGNALS THAT TERMINATE TRANSCRIPTION PREMATURELY. DOWNREGULATION OF GENE EXPRESSION BY EARLY TRANSCRIPTION STOPPAGE OCCURS WIDELY IN CELLS RANGING FROM BACTERIA TO HUMAN, BUT THE UNDERLYING MECHANISM AND SELECTIVITY REMAINS UNCLEAR. THIS RESEARCH PROJECT WILL INVESTIGATE PREMATURE TRANSCRIPTION TERMINATION IN THE YEAST S. CEREVISIAE, A TRACTABLE MODEL FOR STUDYING MANY CONSERVED BIOLOGICAL PROCESSES. UNDERGRADUATE STUDENT RESEARCHERS WILL BE TRAINED TO USE CLASSICAL GENETICS AND MODERN BIOINFORMATIC TOOLS TO DISSECT TRANSCRIPTION STOP SIGNALS AND DISCOVER MUTANTS THAT ALTER RECOGNITION. NEW GENE TARGETS WILL BE IDENTIFIED, WITH A BROADER GOAL OF IDENTIFYING SHARED REGULATORY FEATURES. STUDENT TRAINEES WILL HAVE OPPORTUNITIES TO PRESENT THEIR WORK AT NATIONAL RESEARCH CONFERENCES AND COAUTHOR PUBLICATIONS. THIS RESEARCH WILL ALSO BE INCORPORATED INTO A CORE UNDERGRADUATE BIOLOGY LABORATORY COURSE, MOBILIZING 50 ADDITIONAL STUDENTS TO VALIDATE GENE TARGETS. COURSE RESOURCES WILL BE SHARED BROADLY SO ADDITIONAL EDUCATIONAL COMMUNITIES MAY CONTRIBUTE AND BENEFIT. PREMATURE TRANSCRIPTION TERMINATION (ATTENUATION) OF EUKARYOTIC RNA POLYMERASE II (POL II) IS MORE PREVALENT THAN ONCE APPRECIATED BUT REMAINS ILL-DEFINED. THE INVESTIGATORS HYPOTHESIZE THAT A HYBRID TRANSCRIPTION TERMINATION PATHWAY INVOLVING THE HRP1 RNA-BINDING PROTEIN AND SEN1 HELICASE CONTRIBUTES BROADLY TO YEAST POL II ATTENUATION. THIS RESEARCH PROJECT WILL GENERATE A COMPREHENSIVE GENETIC PROFILE OF TEN NEWLY IDENTIFIED ATTENUATORS AND IDENTIFY THE LARGER REPERTOIRE OF HRP1-DEPENDENT ATTENUATORS ACROSS THE YEAST GENOME. IN AIM 1, A GENETIC SELECTION WILL IDENTIFY CIS-ACTING MUTATIONS THAT DISRUPT ATTENUATOR FUNCTION IN PLASMID-BASED REPORTER GENES, FOLLOWED BY CONFIRMATION IN CRISPR-EDITED GENOMIC DNA. A GENETIC SCREEN WILL PROBE THE EFFECT OF TRANS-ACTING MUTATIONS THAT ALTER TERMINATION FACTOR RECRUITMENT, POL II CTD MODIFICATION, AND POL II PAUSING. A DIRECT MECHANISM WILL BE ASSAYED USING HRP1 MUTANTS DEFECTIVE FOR BINDING RNA OR AFFILIATED PROTEINS. IN AIM 2, AN AUXIN-INDUCIBLE DEGRON SYSTEM WILL DEPLETE HRP1, FOLLOWED BY PRECISION NUCLEAR RUN-ON SEQUENCING (PRO-SEQ) TO MONITOR GENOME-WIDE POL II READ-THROUGH DEFECTS. THIS WORK WILL INFORM ANALYSIS OF THE HRP1 ORTHOLOG HNRNPDL, A HUMAN PROTEIN THAT LIKEWISE BINDS AU-RICH RNA AND REGULATES TRANSCRIPTION. IN ADDITION, ENGINEERED ATTENUATORS MAY BE HARNESSED FOR DYNAMIC GENE CONTROL IN BIOTECHNOLOGY APPLICATIONS, INCLUDING YEAST EXPRESSION OF INDUSTRIAL ENZYMES. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

FUNCTION OF HEMATOPOIETICALLY-DERIVED MYELOID PRECURSORS TO THE CENTRAL NERVOUS S

RUI: DISCOVERING AND CHARACTERIZING THE BINDING DETERMINANTS FOR RNA POLYMERASE-ASSOCIATED PROTEINS IN E. COLI

RUI: DNA AND NANOPARTICLE ASSEMBLIES AS BIOMIMETIC TEMPLATES FOR CALCIUM PHOSPHATE MINERALIZATION

RUI: ELUCIDATING THE MECHANISMS OF SITE SPECIFIC DNA CLEAVAGE USING SINGLE MOLECULE METHODS

EARMARKS

RUI: THE RATE OF EVOLUTION IN STRUCTURED POPULATIONS

EMMANUEL COLLEGE CENTER FOR SCIENCE PARTNERSHIP

IOS PROPOSAL: EFFECTS OF VISION LOSS ON ASTROCYTE MATURATION AND OLIGODENDROCYTE MYELINATION VIA BDNF-ASSOCIATED MECHANISMS IN THE VISUAL CORTEX

DIRECTED GRANTS

RUI: SELECTION AND ASSESSMENT OF BIOMIMETIC TEMPLATES FOR MINERALIZATION

RUI: DEVELOPING MODELS OF FACILITATED DIFFUSION FOR DNA BINDING PROTEINS

EARMARKS

LEAPS-MPS: UNVEILING THE ORIGIN OF CARBON DOT FLUORESCENCE USING DENSITY FUNCTIONAL TIGHT BINDING -IN THIS PROJECT, MANAGED BY THE DIVISION OF CHEMISTRY AT THE NSF, PROFESSOR DUCHIMAZA HEREDIA AND STUDENTS AT EMMANUEL COLLEGE WILL USE COMPUTER SIMULATIONS TO UNDERSTAND WHY CARBON DOTS FLUORESCE. CARBON DOTS ARE FORMED BY A POLYMERIZATION REACTION OF SMALL MOLECULES AT HIGH TEMPERATURES, AND THEY HAVE BEEN OBSERVED TO GLOW IN VARIOUS COLORS. THE MULTICOLOR FLUORESCENCE OF CARBON DOTS MAKES THEM USEFUL IN APPLICATIONS INCLUDING DRUG DELIVERY, BIOSENSING, AND IMAGING. COMPUTATIONAL METHODS WILL BE EMPLOYED TO INVESTIGATE THE REASON FOR FLUORESCENCE, OVERCOMING EXPERIMENTAL CHALLENGES IN DETERMINING THE STRUCTURE OF THE CARBON DOTS. THIS PROJECT WILL CREATE RESEARCH POSITIONS THAT SUPPORT TRAINING FOR UNDERGRADUATE STUDENTS OF DIVERSE BACKGROUNDS AND ESTABLISH PARTNERSHIPS WITH COMPUTATIONAL CHEMISTS AROUND THE BOSTON AREA TO INTRODUCE STUDENTS TO A GRADUATE-LEVEL RESEARCH ENVIRONMENT. THE CHEMISTRY EDUCATION PATHWAY WILL BE STRENGTHENED BY INVOLVING HIGH SCHOOL TEACHERS IN THIS INVESTIGATION AND USING ASPECTS OF THIS PROJECT TO TEACH HIGH SCHOOL STUDENTS HOW COMPUTERS ARE USED IN CHEMISTRY RESEARCH. PROFESSOR DUCHIMAZA HEREDIA AND HIS COMPUTATIONAL CHEMISTRY RESEARCH GROUP WILL INVESTIGATE THE ELECTRONIC NATURE OF MULTICOLOR FLUORESCENCE IN POLYMERIC OR AMORPHOUS CARBON DOTS. EXISTING HYPOTHESES INCLUDE SIZE-DEPENDENT EMISSIONS, SURFACE-STATE DERIVED EMISSION, AND FLUORESCENCE DUE TO MOLECULAR FLUOROPHORES. WHILE FLUORESCENCE ACROSS THE VISIBLE SPECTRUM IS POSSIBLE, EXPERIMENTAL ANALYSIS SUPPORTS ONLY BLUE FLUORESCENCE. THE PROJECT WILL USE ENHANCED SAMPLING METHODS TO PREDICT THE STRUCTURE OF AMORPHOUS CARBON DOTS. IT WILL ALSO LEVERAGE THE CHEMICAL ACCURACY OF DENSITY FUNCTIONAL THEORY (DFT) AND THE SPEED OF DENSITY FUNCTIONAL-BASED TIGHT-BINDING (DFTB). THIS PROJECT AIMS TO DETERMINE WHETHER FLUORESCENCE IS POSSIBLE SOLELY DUE TO THE CARBON DOT STRUCTURE, IDENTIFY HOW THE ENVIRONMENT OF A FLUOROPHORE INFLUENCES ITS EMISSION PROPERTIES, AND PERFORM EXTENSIVE BENCHMARKING TO COMPARE THE RESULTS OF DFT AND DFTB FOR ACCURATE AND FAST PREDICTION OF CARBON DOT AND FLUOROPHORE SYSTEMS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.