First Quarter of 2019
The Burroughs Wellcome Fund’s mission is to advance biomedical science by supporting research and other educational activities. This newsletter is a curated sample of research and activities conducted by recipients of Fund support.
Upcoming grant deadlines:
Graduate Diversity Enrichment Program | Deadline: July 2, 2019
Features
The Conversation (US), 3-22-2019
Boeing 737 Max: The FAA wanted a safe plane – but didn’t want to hurt America’s biggest exporter either
Recent incidents aside, air travel is incredibly safe these days. Global airplane fatalities averaged 840 a year from 2010 to 2018, compared with almost 2,000 in the 1990s. In fact, this decade is on pace to…
Co-author, Susan Webb Yackee has an Innovation in Regulatory Science Award from the Burroughs Wellcome Fund, and her research is also supported by the Russell Sage Foundation.
Cornell Chronicle, 1-10-2019
Hempstead named dean of Weill Cornell Graduate School of Medical Sciences
She (Hempstead) is an elected member of the American Society for Clinical Investigation – where she was also a national counselor – and the American Association of Physicians, and served on the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Board of Scientific Councilors.
Hempstead is a past recipient of the Irma T. Hirschl/Monique Weill-Caulier Trust Award and Burroughs Wellcome Clinical Scientist Award in Translational Research.
Research
EurekAlert!, 3-28-2019
Researchers at Dana-Farber/Boston Children’s optimize gene editing for SCD and beta thalassemia
The work was supported by the Translational Research Program at Boston Children’s Hospital, the National Institutes of Health (NHLBI, NHGRI, NIAID, NIGMS, NIDDK), bluebird bio, the Harvard Stem Cell Institute, the St. Jude Children’s Research Hospital Collaborative Research Consortium, the Burroughs Wellcome Fund, the American Society of Hematology and the Doris Duke Charitable, Charles H. Hood and Cooley’s Anemia Foundations.
New strategy for editing blood stem cells is more efficient and targeted.
EurekAlert!, 3-22-2019
UTSW researchers identify new mechanism to reduce inflammation
The research received support from the National Institutes of Health, The Welch Foundation, the Burroughs Wellcome Fund, the Howard Hughes Medical Institute, and the Simons Foundation.
UT Southwestern researchers have identified two proteins that act as gatekeepers to dampen a potentially life-threatening immune response to chronic infection.
PLOS Pathogens, 3-21-2019
Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans
TMH is supported by NIH/NIAID grant R01 AI093808 and a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease Award.
Overall, our findings indicate that C. neoformans can subvert the fungicidal potential of IM to enable the progression of infection through a mechanism that is not dependent on lymphocyte priming, eosinophil recruitment, or downstream M2 macrophage polarization pathways. These results give us new insight into the plasticity of IM function during fungal infections and the level of control that C. neoformans can exert on host immune responses.
Harvard Gazette, 3-21-2019
Immunotherapy reduced risk of skin cancer development by almost 75 percent
The study was supported by National Institutes of Health grants K08 AR068619 and DP5 OD0213530, and grants from the Burroughs Wellcome Fund, the Sidney Kimmel Foundation, and the Cancer Research Institute. Cornelius and Demehri are co-inventors on a filed patent for calcipotriol plus 5-FU to treat precancerous skin lesions.
Immunotherapy of precancerous skin lesions may prevent squamous cell carcinoma
PLOS Pathogens, 3-20-2019
Bacterial fitness in chronic wounds appears to be mediated by the capacity for high-density growth, not virulence or biofilm functions
P.K.S. was supported by grants from NIH (R01AI101307 and K24HL102246), Defense Threat Reduction Agency Grant HDTRA1-14-1-0018, the Cystic Fibrosis Foundation, and the Burroughs Wellcome Fund.
These data shed light on the bacterial functions needed in chronic wound infections, the nature of stresses applied to bacteria at chronic infection sites, and suggest therapeutic targets that might compromise wound infection pathogenesis.
Frontiers, 3-19-2019
Genetic Modification of Closely Related Candida Species
This work was supported by a Human Frontier Science Program grant to EM, a UC-MEXUS grant to EM, National Institutes of Health grants AI083311 and AI049187 to AJ, AI081704 to RB, PRODEP grant 511-6/17-7433 to EM, CONACyT grant CB-2016-01 282511 to EM, a PATH award from the Burroughs Wellcome Fund to RB and a Welcome Trust Seed Award in Science to EM.
The strains were generated in two different genetic backgrounds for each species — one for which the genomic sequence is available and a second clinically important one. In addition, we have adapted plasmids developed to delete genes and epitope/fluorophore tag proteins in C. albicans so that they can be employed in C. tropicalis. The tools generated here allow for efficient genetic modification of C. dubliniensis and C. tropicalis, and thus facilitate the study of the molecular basis of pathogenesis in these medically relevant fungi.
Nature, 3-18-2019
Sequencing-based methods and resources to study antimicrobial resistance
A.W.D. received support from the Institutional Program Unifying Population and Laboratory-Based Sciences Burroughs Wellcome Fund Grant to Washington University.
This Review provides a detailed overview of antimicrobial resistance identification and characterization methods, from traditional antimicrobial susceptibility testing to recent deep-learning methods. We focus on sequencing-based resistance discovery and discuss tools and databases used in antimicrobial resistance studies.
EurekAlert!, 2-28-2019
‘Mutation hotspot’ allows common fungus to adapt to different host environments
The National Institutes of Health (grants AI081704/AI141893) and the Burroughs Wellcome Fund supported the research.
New research from Brown University helps show how this fungus gets the flexibility to live in these vastly different environments.
EurekAlert!, 2-28-2019
‘Mutation hotspot’ allows common fungus to adapt to different host environments
The research was supported by the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Sequencing Facility at Johns Hopkins, the Johns Hopkins Clinician Scientist Career Development Award, the Burroughs Wellcome Fund Career Awards for Medical Scientists, the Doris Duke Charitable Foundation (2014107), the Department of Neurosurgery at Johns Hopkins and the National Cancer Institute (P50- CA062924).
By sequencing the entire genomes of tumor cells from six people with a rare cancer of the nose and sinus cavity, Johns Hopkins researchers report they unexpectedly found the same genetic change (one in a gene involved in muscle formation) in five of the tumors.
Nature, 2-26-2019
CRISPResso2 provides accurate and rapid genome editing sequence analysis
D.R.L. is supported by DARPA HR0011-17-2-0049; US NIH RM1 HG009490, R01 EB022376 and R35 GM118062; and the HHMI. J.K.J. is supported by DARPA HR0011-17-2-0042, NIH R35 GM118158 and NIH RM1 HG009490. D.E.B. is supported by the NIDDK (R03DK109232), NHLBI (DP2OD022716, P01HL32262), Burroughs Wellcome Fund, Doris Duke Charitable Foundation and St. Jude Children’s Research Hospital Collaborative Research Consortium. L.P. is supported by NHGRI (R00HG008399), DARPA HR0011-17-2-0042, and the Centers for Excellence in Genomic Science of the National Institutes of Health under award number RM1HG009490 through a New Collaborator Grant subaward.
Nature, 2-21-2019
A platform for glycoengineering a polyvalent pneumococcal bioconjugate vaccine using E. coli as a host
C.L.S. was supported by a Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease award.
These proof-of-principle experiments establish a platform to overcome limitations of other conjugating enzymes enabling the development of bioconjugate vaccines for many important human and animal pathogens.
EurekAlert!, 2-19-2019
Fluorescing urine signals organ transplant rejection, could replace needle biopsies
Kwong and Adams published the study’s results in the journal Nature Biomedical Engineering on February 18, 2019. The research was funded by the National Institutes of Health, the National Science Foundation and the Burroughs Wellcome Fund.
New nanoparticle makes urine glow as soon as T cells initiate an attack on transplanted organs
Frontiers, 2-19-2019
Mapping the Fungal Battlefield: Using in situ Chemistry and Deletion Mutants to Monitor Interspecific Chemical Interactions Between Fungi
Research in AR’s lab is also supported by the National Science Foundation (DEB-1442113), the Guggenheim Foundation, and the Burroughs Wellcome Fund.
To evaluate these, and to gain insight into the secondary metabolic arsenal fungi possess, we co-cultured Aspergillus fischeri, a genetically tractable fungus that produces a suite of mycotoxins, with Xylaria cubensis, a fungus that produces the fungistatic compound and FDA-approved drug, griseofulvin.
The Journal of Biological Chemistry, 2-19-2019
Importance of a tRNA anticodon loop modification and a conserved, noncanonical anticodon stem pairing in tRNACGGPro for decoding
Christine M. Dunham is a Burroughs Wellcome Fund Pathogenesis of Infectious Diseases Fellow.
Our results reveal how the tRNA modification at nucleotide 37 stabilizes interactions with the mRNA codon to preserve the mRNA frame.
EurekAlert!, 2-18-2019
Fetal signaling pathways may offer future targets for treating lung injury
Funding for this study came from the National Institutes of Health (HL007915, HD043245, HL140129, HL110942, HL132999, HL129478, HL134745), the Parker B. Francis Foundation, the Pulmonary Hypertension Association, Burroughs Wellcome, the National Science Foundation, and the Gilead Research Scholars Foundation.
Specialized lung cells appearing very early in development are key
EurekAlert!, 2-18-2019
Specialized lung cells appear very early in development
Funding for this study came from the National Institutes of Health (grants HL007915, HD043245, HL140129, HL110942, HL132999, HL129478, and HL134745), the Parker B. Francis Foundation, the Pulmonary Hypertension Association, Burroughs Wellcome, the National Science Foundation and the Gilead Research Scholars Foundation.
CHOP/Penn researchers: Fetal signaling pathways may offer future targets for treating lung injury
PLOS Genetics, 2-15-2019
Modular epistasis and the compensatory evolution of gene deletion mutants
S.K. acknowledges support from the Burroughs Wellcome Fund Career Award at Scientific Interface (Grant 1010719.01), the Alfred P. Sloan Foundation (Grant FG-2017-9227) and the Hellman Foundation. M.M.D. acknowledges support from the Simons Foundation (Grant 376196), grant DEB-1655960 from the NSF, and grant GM104239 from the NIH.
Our results suggest that genotypes with similar epistatic interactions with gene deletion mutations will also have similar epistatic interactions with adaptive mutations, meaning that genome scale maps of epistasis between gene deletion mutations can be predictive of evolutionary dynamics.
Futurity.org, 2-14-2019
Fluorescent tags light up when proteins misfold
This work had funding from the National Science Foundation, the Burroughs Wellcome Fund, Penn State, the Penn State Huck Institutes of the Life Sciences, and the National Institutes of Health.
A new method uses fluorescence to detect potentially disease-causing forms of proteins as they unravel due to stress or mutations.
Penn State University, 2-13-2019
A new method uses fluorescence to detect potentially disease-causing forms of proteins as they unravel due to stress or mutations.
This work had funding from the National Science Foundation, the Burroughs Wellcome Fund, Penn State, the Penn State Huck Institutes of the Life Sciences, and the National Institutes of Health.
A new method uses fluorescence to detect potentially disease-causing forms of proteins as they unravel due to stress or mutations.
Massachusetts General Hospital, 2-11-2019
Interaction between immune factors triggers cancer-promoting chronic inflammation
Support for the study includes National Institutes of Health grants K08 AR068619 and DP5 OD021353 and grants from the Burroughs Wellcome Fund, the Sidney Kimmel Foundation, the Cancer Research Institute, and the Howard Hughes Medical Research Fellows Program.
Mass. General study finds that blocking IL-33/Treg axis prevents development of skin and colon cancer in mice with chronic inflammation
Nature, 2-8-2019
Design, execution, and analysis of CRISPR–Cas9-based deletions and genetic interaction networks in the fungal pathogen Candida albicans
This work was supported by an NSERC Discovery Grant, an NSERC Discovery Accelerator Supplement, and a Banting Research Foundation Discovery Award to R.S.S. A.C. was supported by the Burroughs Wellcome Fund Career Award for Medical Scientists.
This protocol overcomes previous limitations associated with genetic manipulation in C. albicans and advances researchers’ ability to perform genetic analysis in this pathogen; the protocol also has broad applicability to other mating-competent microorganisms.
Broad Institute, 2-1-2019
New microfluidics platform separates cell types for RNA profiling
Funding for this study was provided in part by the National Institute of Allergy and Infectious Disease (U24 AI118668) and the Burroughs Wellcome Fund.
Prototype technology demonstrates a more automated, efficient, and scalable workflow to analyze cells by type
EurekAlert!, 1-31-2019
An Unexpected Mode of Action for an Antibody
This study was supported by the National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Pew Biomedical Scholars Award, Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, The Netherlands Organization for Scientific Research, European Molecular Biology Organisation, Zoonoses Anticipation and Preparedness Initiative, Pasteur Institute, Centre National de la Recherche Scientifique, LabEx Integrative Biology of Emerging Infectious Diseases. University of Washington Arnold and Mabel Beckman cryoEM Center, UW Proteomics Resource, and beamline 5.0.1 at the Advanced Light Source, Lawrence Berkeley National Laboratory.
Visualizing how some patients successfully fought off deadly coronaviruses could pave the way to combat these respiratory infections.
EurekAlert!, 1-24-2019
New theory unlocks the secret behind protein-membrane interactions
This study was supported by the Burroughs Wellcome Fund Career Award at the Scientific Interface, a National Science Foundation Career Award (#1054832), and the MU Research Board. The computations were performed on MU’s RCSS HPC infrastructure (NSF grant #CNS-1429294).
MU researchers gain a greater understanding of cell behavior by developing theoretical model of how proteins work with cell membranes.
EurekAlert!, 1-16-2019
Experimental treatment approach shows potential against Staphylococcus aureus
Torres is also a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases.
A new class of engineered proteins may counter infection caused by Staphylococcus aureus – a bacterial species considered one of the largest global health threats, a new study suggests.
EurekAlert!, 1-14-2019
Herpes viruses and tumors evolved to learn how to manipulate the same ancient RNA
Researchers from Massachusetts General Hospital and the Simons Center for Systems Biology at the Institute for Advanced Study also contributed to this work. This research received funding from the National Institutes of Health (AI112951), the American Cancer Society(PF-14-116-01 MPC), the V Foundation, Stand Up to Cancer, the National Science Foundation, and the Lustgarten Foundation, the Pershing Square Sohn Research Alliance, the Mark Foundation, the Burroughs Wellcome Fund, and Affymetrix, Inc.
Findings could have implications for drugs and insight into diseases like Alzheimer’s.
EurekAlert!, 1-7-2019
New study of MRSA spread provides framework for community-based infection surveillance
Researchers from Massachusetts General Hospital and the Simons Center for Systems Biology at the Institute for Advanced Study also contributed to this work. This research received funding from the National Institutes of Health (AI112951), the American Cancer Society(PF-14-116-01 MPC), the V Foundation, Stand Up to Cancer, the National Science Foundation, and the Lustgarten Foundation, the Pershing Square Sohn Research Alliance, the Mark Foundation, the Burroughs Wellcome Fund, and Affymetrix, Inc.
Findings could have implications for drugs and insight into diseases like Alzheimer’s.
Education
McDowellNews.com, 3-21-2019
$175K boost for science: West Marion teacher lands major grant
On Monday, West Marion fifth-grade science teacher Renata Crawley was awarded the 2019 Career Award for Science and Mathematics Teachers by the Burroughs Wellcome Fund.
A West Marion Elementary educator dedicated to teaching kids about outdoor science and the environment received a five-year $175,000 grant from a biomedical research foundation.
WRAL.com, 2-20-2019
How the ‘little’ Washington seeks inclusion and celebrates diversity
In August 2018, Inner Banks STEM received one of two $179,000 Burroughs Wellcome Grants.
“We just made a conscientious decision here in our area that [STEM] is what we were going to focus on,” Powell explained. “With the STEM component being in our name, there’s no mistaking the fact that we are about science, technology, engineering and math.
EducationNC, 2-20-2019
The positive force of “bridge builders” across North Carolina
Freebird McKinney is Burroughs Wellcome Fund 2018 N.C. Teacher of the Year. He is a social studies and philosophy teacher at Walter M. Williams High School.
It will require all of us to transcend the walls of this room and to work collaboratively to achieve the ultimate goal of reclaiming North Carolina as “First in Teaching.”
Sampson Independent, 1-29-2019
STEM Partnership Launches
I-40 E.A.S.T. is a student STEM program that will bring engineering, agriculture, science and technology to students through a two-year project that is facilitated by UNCW and funded by the Burroughs Wellcome Student STEM Enrichment Program and engages students from communities in the Southeastern portion of the state.
A partnership between Clinton City Schools and the University of North Carolina at Wilmington is bringing an enrichment program to local middle school students.
EducationNC, 1-24-2019
Public School Forum releases top education priorities at annual breakfast
Burroughs Wellcome Fund’s 2018 NC Teacher of the Year Freebird McKinney opened by talking about his own experience as a Charlotte-Mecklenburg student joining hands with classmates and singing “We are the World” as a pre-requisite to recess.
As the legislature returns to session, education advocates are making their priorities clear. For the Public School Forum of North Carolina, that’s traditional public schools — their funding, their teachers and leaders, their diversity, their students.
The Daily Advance, 1-8-2019
NEAAAT robotics team gears up for FIRST tournament
The department’s grant funding from NASA, the Burroughs Wellcome Fund, the Golden LEAF Foundation, and the NC Space Grant support robot construction and support costs for the team to attend tournament competitions.
The Northeast Academy for Aerospace and Advanced Technology is diving deep into competition robotics in its first year as part of the FIRST Robotics Competition.
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