Advertisements
Feeds:
Posts
Comments

Archive for the ‘Single Cell Genomics’ Category


Single-cell Genomics: Directions in Computational and Systems Biology – Contributions of Prof. Aviv Regev @Broad Institute of MIT and Harvard, Cochair, the Human Cell Atlas Organizing Committee with Sarah Teichmann of the Wellcome Trust Sanger Institute

 

Curator: Aviva Lev-Ari, PhD, RN

 

Dana Pe’er, PhD, now chair of computational and systems biology at the Sloan Kettering Institute at the Memorial Sloan Kettering Cancer Center and a member of the Human Cell Atlas Organizing Committee,

what really sets Regev apart is the elegance of her work. Regev, says Pe’er, “has a rare, innate ability of seeing complex biology and simplifying it and formalizing it into beautiful, abstract, describable principles.”

Dr. Aviv Regev, an MIT biology professor who is also chair of the faculty of the Broad and director of its Klarman Cell Observatory and Cell Circuits Program, was reviewing a newly published white paper detailing how the Human Cell Atlas is expected to change the way we diagnose, monitor, and treat disease at a gathering of international scientists at Israel’s Weizmann Institute of Science, 10/2017.

For Regev, the importance of the Human Cell Atlas goes beyond its promise to revolutionize biology and medicine. As she once put it, without an atlas of our cells, “we don’t really know what we’re made of.”

Regev, turned to a technique known as RNA interference (she now uses CRISPR), which allowed her to systematically shut genes down. Then she looked at which genes were expressed to determine how the cells’ response changed in each case. Her team singled out 100 different genes that were involved in regulating the response to the pathogens—some of which weren’t previously known to be involved in immune function. The study, published in Science, generated headlines.

The project, the Human Cell Atlas, aims to create a reference map that categorizes all the approximately 37 trillion cells that make up a human. The Human Cell Atlas is often compared to the Human Genome Project, the monumental scientific collaboration that gave us a complete readout of human DNA, or what might be considered the unabridged cookbook for human life. In a sense, the atlas is a continuation of that project’s work. But while the same DNA cookbook is found in every cell, each cell type reads only some of the recipes—that is, it expresses only certain genes, following their DNA instructions to produce the proteins that carry out a cell’s activities. The promise of the Human Cell Atlas is to reveal which specific genes are expressed in every cell type, and where the cells expressing those genes can be found.

Regev says,

The final product, will amount to nothing less than a “periodic table of our cells,” a tool that is designed not to answer one specific question but to make countless new discoveries possible.

Sequencing the RNA of the cells she’s studying can tell her only so much. To understand how the circuits change under different circumstances, Regev subjects cells to different stimuli, such as hormones or pathogens, to see how the resulting protein signals change.

“the modeling step”—creating algorithms that try to decipher the most likely sequence of molecular events following a stimulus. And just as someone might study a computer by cutting out circuits and seeing how that changes the machine’s operation, Regev tests her model by seeing if it can predict what will happen when she silences specific genes and then exposes the cells to the same stimulus.

By sequencing the RNA of individual cancer cells in recent years—“Every cell is an experiment now,” she says—she has found remarkable differences between the cells of a single tumor, even when they have the same mutations. (Last year that work led to Memorial Sloan Kettering’s Paul Marks Prize for Cancer Research.) She found that while some cancers are thought to develop resistance to therapy, a subset of melanoma cells were resistant from the start. And she discovered that two types of brain cancer, oligodendroglioma and astrocytoma, harbor the same cancer stem cells, which could have important implications for how they’re treated.

As a 2017 overview of the Human Cell Atlas by the project’s organizing committee noted, an atlas “is a map that aims to show the relationships among its elements.” Just as corresponding coastlines seen in an atlas of Earth offer visual evidence of continental drift, compiling all the data about our cells in one place could reveal relationships among cells, tissues, and organs, including some that are entirely unexpected. And just as the periodic table made it possible to predict the existence of elements yet to be observed, the Human Cell Atlas, Regev says, could help us predict the existence of cells that haven’t been found.

This year alone it will fund 85 Human Cell Atlas grants. Early results are already pouring in.

  • In March, Swedish researchers working on cells related to human development announced they had sequenced 250,000 individual cells.
  • In May, a team at the Broad made a data set of more than 500,000 immune cells available on a preview site.

The goal, Regev says, is for researchers everywhere to be able to use the open-source platform of the Human Cell Atlas to perform joint analyses.

Eric Lander, PhDthe founding director and president of the Broad Institute and a member of the Human Cell Atlas Organizing Committee, likens it to genomics.

“People thought at the beginning they might use genomics for this application or that application,” he says. “Nothing has failed to be transformed by genomics, and nothing will fail to be transformed by having a cell atlas.”

“How did we ever imagine we were going to solve a problem without single-cell resolution?”

SOURCE

https://www.technologyreview.com/s/611786/the-cartographer-of-cells/?utm_source=MIT+Technology+Review&utm_campaign=Alumni-Newsletter_Sep-Oct-2018&utm_medium=email

Other related articles published in this Open Access Online Scientific Journal include the following:

 

University of California Santa Cruz’s Genomics Institute will create a Map of Human Genetic Variations

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/01/13/university-of-california-santa-cruzs-genomics-institute-will-create-a-map-of-human-genetic-variations/

 

Recognitions for Contributions in Genomics by Dan David Prize Awards

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/31/recognitions-for-contributions-in-genomics-by-dan-david-prize-awards/

 

ENCODE (Encyclopedia of DNA Elements) program: ‘Tragic’ Sequestration Impact on NHGRI Programs

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/18/encode-encyclopedia-of-dna-elements-program-tragic-sequestration-impact-on-nhgri-programs/

 

Single-cell Sequencing

Genomic Diagnostics: Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single Molecule DNA Sequencing

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/04/genomic-diagnostics-three-techniques-to-perform-single-cell-gene-expression-and-genome-sequencing-single-molecule-dna-sequencing/

 

LIVE – Real Time – 16th Annual Cancer Research Symposium, Koch Institute, Friday, June 16, 9AM – 5PM, Kresge Auditorium, MIT – See, Aviv Regev

REAL TIME PRESS COVERAGE & Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/03/13/16th-annual-cancer-research-symposium-koch-institute-friday-june-16-9am-5pm-kresge-auditorium-mit/

 

LIVE 11/3/2015 1:30PM @The 15th Annual EmTech MIT – MIT Media Lab: Top 10 Breakthrough Technologies & 2015 Innovators Under 35 – See, Gilead Evrony

REAL TIME PRESS COVERAGE & Reporter: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2015/11/03/live-1132015-130pm-the-15th-annual-emtech-mit-mit-media-lab-top-10-breakthrough-technologies-2015-innovators-under-35/

 

Cellular Guillotine Created for Studying Single-Cell Wound Repair

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2017/06/29/cellular-guillotine-created-for-studying-single-cell-wound-repair/

 

New subgroups of ILC immune cells discovered through single-cell RNA sequencing

Reporter: Stephen J Williams, PhD

https://pharmaceuticalintelligence.com/2016/02/17/new-subgroups-of-ilc-immune-cells-discovered-through-single-cell-rna-sequencing-from-karolinska-institute/

 

#JPM16: Illumina’s CEO on new genotyping array called Infinium XT and Bio-Rad Partnership for single-cell sequencing workflow

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/12/jpm16-illuminas-ceo-on-new-genotyping-array-called-infinium-xt-and-bio-rad-partnership-for-single-cell-sequencing-workflow/

 

Juno Acquires AbVitro for $125M: high-throughput and single-cell sequencing capabilities for Immune-Oncology Drug Discovery

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/12/juno-acquires-abvitro-for-125m-high-throughput-and-single-cell-sequencing-capabilities-for-immune-oncology-drug-discovery/

 

NIH to Award Up to $12M to Fund DNA, RNA Sequencing Research: single-cell genomics,  sample preparation,  transcriptomics and epigenomics, and  genome-wide functional analysis.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/10/27/nih-to-award-up-to-12m-to-fund-dna-rna-sequencing-research-single-cell-genomics-sample-preparation-transcriptomics-and-epigenomics-and-genome-wide-functional-analysis/

 

Genome-wide Single-Cell Analysis of Recombination Activity and De Novo Mutation Rates in Human Sperm

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

https://pharmaceuticalintelligence.com/2012/08/07/genome-wide-single-cell-analysis-of-recombination-activity-and-de-novo-mutation-rates-in-human-sperm/

REFERENCES to Original studies

In Science, 2018

Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors

 See all authors and affiliations

Science  21 Apr 2017:
Vol. 356, Issue 6335, eaah4573
DOI: 10.1126/science.aah4573
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis

See all authors and affiliations

Science  26 Apr 2018:
eaar3131
DOI: 10.1126/science.aar3131

In Nature, 2018 and 2017

How to build a human cell atlas

Aviv Regev is a maven of hard-core biological analyses. Now she is part of an effort to map every cell in the human body.

  1. Research | 

  2. Research | 

  3. Research | 

  4. Research | 

  5. Research | 

  6. Amendments and Corrections | 

  7. Research |  | OPEN

  8. Research | 

  9. Amendments and Corrections | 

  10. Comments and Opinion | 

  11. Research | 
Advertisements

Read Full Post »


Emerging STAR in Molecular Biology, Synthetic Virology and Genomics: Clodagh C. O’Shea: ChromEMT – Visualizing 3D chromatin structure

 

Curator: Aviva Lev-Ari, PhD, RN

 

On 8/28/2017, I attend and covered in REAL TIME the CHI’s 5th Immune Oncology Summit – Oncolytic Virus Immunotherapy, August 28-29, 2017 Sheraton Boston Hotel | Boston, MA

https://pharmaceuticalintelligence.com/2017/08/28/live-828-chis-5th-immune-oncology-summit-oncolytic-virus-immunotherapy-august-28-29-2017-sheraton-boston-hotel-boston-ma/

 

I covered in REAL TIME this event and Clodagh C. O’Shea talk at the conference.

On that evening, I e-mailed my team that

“I believe that Clodagh C. O’Shea will get the Nobel Prizebefore CRISPR

 

11:00 Synthetic Virology: Modular Assembly of Designer Viruses for Cancer Therapy

Clodagh_OShea

Clodagh O’Shea, Ph.D., Howard Hughes Medical Institute Faculty Scholar; Associate Professor, William Scandling Developmental Chair, Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies

Design is the ultimate test of understanding. For oncolytic therapies to achieve their potential, we need a deep mechanistic understanding of virus and tumor biology together with the ability to confer new properties.

To achieve this, we have developed

  • combinatorial modular genome assembly (ADsembly) platforms,
  • orthogonal capsid functionalization technologies (RapAd) and
  • replication assays that have enabled the rational design, directed evolution, systematic assembly and screening of powerful new vectors and oncolytic viruses.

 

Clodagh O’Shea’s Talk In Real Time:

  • Future Cancer therapies to be sophisticated as Cancer is
  • Targer suppresor pathways (Rb/p53)
  • OV are safe their efficacy ishas been limited
  • MOA: Specify Oncolytic Viral Replication in Tumor cells Attenuate – lack of potency
  • SOLUTIONS: Assembly: Assmble personalized V Tx fro libraries of functional parts
  • Adenovirus – natural & clinical advantages
  • Strategy: Technology for Assmbling Novel Adenovirus Genomes using Modular Genomic Parts
  • E1 module: Inactives Rb & p53
  • core module:
  • E3 Module Immune Evasion Tissue targeting
  • E4 Module Activates E2F (transcription factor TDP1/2), PI3K
  • Adenovirus promoters for Cellular viral replication — Tumor Selective Replication: Novel Viruses Selective Replicate in RB/p16
  • Engineering Viruses to overcome tumor heterogeneity
  • Target multiple & Specific Tumor Cel Receptors – RapAd Technology allows Re-targeting anti Rapamycin – induced targeting of adenovirus
  • Virus Genome: FKBP-fusion FRB-Fiber
  • Engineer Adenovirus Caspids that prevent Liver uptake and Sequestration – Natural Ad5 Therapies 
  • Solution: AdSyn335 Lead candidat AdSyn335 Viruses targeting multiple cells
  • Engineering Mutations that enhanced potency
  • Novel Vector: Homes and targets
  • Genetically engineered PDX1 – for Pancreatic Cancer Stroma: Early and Late Stage
On Twitter:

Engineer Adenovirus Caspids prevent Liver uptake and Sequestration – Natural Ad5 Therapies C. O’Shea, HHDI

Scientist’s Profile: Clodagh C. O’Shea

http://www.salk.edu/scientist/clodagh-oshea/

EDUCATION

BS, Biochemistry and Microbiology, University College Cork, Ireland
PhD, Imperial College London/Imperial Cancer Research Fund, U.K.
Postdoctoral Fellow, UCSF Comprehensive Cancer Center, San Francisco, U.S.A

VIDEOS

http://www.salk.edu/scientist/clodagh-oshea/videos/

O’Shea Lab @Salk

http://oshea.salk.edu/

AWARDS & HONORS

  • 2016 Howard Hughes Medical Institute Faculty Scholar
  • 2014 W. M. Keck Medical Research Program Award
  • 2014 Rose Hills Fellow
  • 2011Science/NSF International Science & Visualization Challenge, People’s Choice
  • 2011 Anna Fuller Award for Cancer Research
  • 2010, 2011, 2012 Kavli Frontiers Fellow, National Academy of Sciences
  • 2009 Sontag Distinguished Scientist Award
  • 2009 American Cancer Society Research Scholar Award
  • 2008 ACGT Young Investigator Award for Cancer Gene Therapy
  • 2008 Arnold and Mabel Beckman Young Investigator Award
  • 2008 William Scandling Assistant Professor, Developmental Chair
  • 2007 Emerald Foundation Schola

READ 

Clodagh C. O’Shea: ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells | Science

http://science.sciencemag.org/content/357/6349/eaag0025

and 

https://www.readbyqxmd.com/keyword/93030

Clodagh C. O’Shea

In Press

Jul 27, 2017 – Salk scientists solve longstanding biological mystery of DNA organization

Sep 22, 2016 – Clodagh O’Shea named HHMI Faculty Scholar for groundbreaking work in designing synthetic viruses to destroy cancer

Oct 05, 2015 – Clodagh O’Shea awarded $3 million to unlock the “black box” of the nucleus

Aug 27, 2015 – The DNA damage response goes viral: a way in for new cancer treatments

Apr 12, 2013 – Salk Institute promotes three top scientists

Oct 16, 2012 – Cold viruses point the way to new cancer therapies

Aug 25, 2010 – Use the common cold virus to target and disrupt cancer cells?

Oct 22, 2009 – Salk scientist receives The Sontag Foundation’s Distinguished Scientist Award

May 15, 2008 – Salk scientist wins 2008 Beckman Young Investigator Award

Mar 24, 2008 – Salk scientist wins 2007 Young Investigator’s Award in Gene Therapy for Cancer

Read Full Post »