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Archive for the ‘Interviews with Scientific Leaders’ Category

Cancer Policy Related News from Washington DC and New NCI Appointments

Reportor: Stephen J. Williams, PhD.

Biden to announce appointees to Cancer Panel, part of initiative to cut death rate

The president first launched the initiative in 2016 as vice president.

By Mary Kekatos

July 13, 2022, 3:00 PM

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America This Morning

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President Joe Biden will announce Wednesday his appointees to the President’s Cancer Panel, ABC News can exclusively reveal.

The Cancer Panel is part of Biden’s Cancer Moonshot Initiative, which was relaunched in February, with a goal of slashing the national cancer death rate by 50% over the next 25 years.MORE: Biden relaunches cancer ‘moonshot’ initiative to help cut death rate

Biden will appoint Dr. Elizabeth Jaffee, Dr. Mitchel Berger and Dr. Carol Brown to the panel, which will advise him and the White House on how to use resources of the federal government to advance cancer research and reduce the burden of cancer in the United States.

Jaffee, who will serve as chair of the panel, is an expert in cancer immunology and pancreatic cancer, according to the White House. She is currently the deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and previously led the American Association for Cancer Research.

PHOTO: In this Sept. 8, 2016, file photo, Dr. Elizabeth M. Jaffee of the Pancreatic Dream Team attends Stand Up To Cancer (SU2C), a program of the Entertainment Industry Foundation (EIF), in Hollywood, Calif.
In this Sept. 8, 2016, file photo, Dr. Elizabeth M. Jaffee of the Pancreatic Dream Team attends Stand Up To Cancer (SU2C), a program of the Entertainment Industry Foundation (EIF), in Hollywood, Calif.ABC Handout via Getty Images, FILE

Berger, a neurological surgeon, directs the University of California, San Francisco Brain Tumor Center and previously spent 23 years at the school as a professor of neurological surgery.

Brown, a gynecologic oncologist, is the senior vice president and chief health equity officer at Memorial Sloan Kettering Cancer Center in New York City. According to the White House, much of her career has been focused on eliminating cancer care disparities due to racial, ethnic, cultural or socioeconomic factors.

Additionally, First Lady Jill Biden, members of the Cabinet and other administration officials are holding a meeting Wednesday of the Cancer Cabinet, made up of officials across several governmental departments and agencies, the White House said.

The Cabinet will introduce new members and discuss priorities in the battle against cancer including closing the screening gap, addressing potential environmental exposures, reducing the number of preventable cancer and expanding access to cancer research.MORE: Long Island school district found to have higher rates of cancer cases: Study

It is the second meeting of the cabinet since Biden relaunched the initiative in February, which he originally began in 2016 when he was vice president.

Both Jaffee and Berger were members of the Blue Ribbon Panel for the Cancer Moonshot Initiative led by Biden.

The initiative has personal meaning for Biden, whose son, Beau, died of glioblastoma — one of the most aggressive forms of brain cancer — in 2015.

“I committed to this fight when I was vice president,” Biden said at the time, during an event at the White House announcing the relaunch. “It’s one of the reasons why, quite frankly, I ran for president. Let there be no doubt, now that I am president, this is a presidential, White House priority. Period.”

The initiative has several priority actions including diagnosing cancer sooner; preventing cancer; addressing inequities; and supporting patients, caregivers and survivors.

PHOTO: In this June 14, 2016, file photo, Dr. Carol Brown, physician at Memorial Sloan Kettering Cancer Center, gives a presentation, at The White House Summit on The United State of Women, in Washington, D.C.
In this June 14, 2016, file photo, Dr. Carol Brown, physician at Memorial Sloan Kettering Cancer Center, gives a presentation, at The White House Summit on The United State of Women, in Washington, D.C.NurPhoto via Getty Images, FILE

The White House has also issued a call to action to get cancer screenings back to pre-pandemic levels.

More than 9.5 million cancer screenings that would have taken place in 2020 were missed due to the COVID-19 pandemic, according to the National Institutes of Health.MORE: Louisiana’s ‘Cancer Alley’ residents in clean air fight

“We have to get cancer screenings back on track and make sure they’re accessible to all Americans,” Biden said at the time.

Since the first meeting of the Cancer Cabinet, the Centers for Disease Control and Prevention has issued more than $200 million in grants to cancer prevention programs, the Centers for Medicaid & Medicare Services implemented a new model to reduce the cost of cancer care, and the U.S. Patent and Trademark Office said it will fast-track applications for cancer immunotherapies.

ABC News’ Sasha Pezenik contributed to this report.

Biden to tap prominent Harvard cancer surgeon to head National Cancer Institute

Monica Bertagnolli brings leadership experience in cancer clinical trials funded by the $7 billion research agency

headshot of Monica Bertagnolli
Monica BertagnolliASCO; GLENN DAVENPORT

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President Joe Biden is expected to pick cancer surgeon Monica Bertagnolli as the next director of the National Cancer Institute (NCI). Bertagnolli, a physician-scientist at Brigham and Women’s Hospital, the Dana-Farber Cancer Center, and Harvard Medical School, specializes in gastrointestinal cancers and is well known for her expertise in clinical trials. She will replace Ned Sharpless, who stepped down as NCI director in April after nearly 5 years.

The White House has not yet announced the selection, first reported by STAT, but several cancer research organizations closely watching for the nomination have issued statements supporting Bertagnolli’s expected selection. She is “a national leader” in clinical cancer research and “a great person to take the job,” Sharpless told ScienceInsider.

With a budget of $7 billion, NCI is the largest component of the National Institutes of Health (NIH) and the world’s largest funder of cancer research. Its director is the only NIH institute director selected by the president. Bertagnolli’s expected appointment, which does not require Senate confirmation, drew applause from the cancer research community

Margaret Foti, CEO of the American Association for Cancer Research, praised Bertagnolli’s “appreciation for … basic research” and “commitment to ensuring that such treatment innovations reach patients … across the United States.” Ellen Sigal, chair and founder of Friends of Cancer Research, says Bertagnolli “brings expertise the agency needs at a true inflection point for cancer research.”

Bertagnolli, 63, will be the first woman to lead NCI. Her lab research on tumor immunology and the role of a gene called APC in colorectal cancer led to a landmark trial she headed showing that an anti-inflammatory drug can help prevent this cancer. In 2007, she became the chief of surgery at the Dana-Farber Brigham Cancer Center.

She served as president of the American Society of Clinical Oncology in 2018 and currently chairs the Alliance for Clinical Trials in Oncology, which is funded by NCI’s National Clinical Trials Network. The network is a “complicated” program, and “Monica will have a lot of good ideas on how to make it work better,” Sharpless says.

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One of Bertagnolli’s first tasks will be to shape NCI’s role in Biden’s reignited Cancer Moonshot, which aims to slash the U.S. cancer death rate in half within 25 years. NCI’s new leader also needs to sort out how the agency will mesh with a new NIH component that will fund high-risk, goal-driven research, the Advanced Research Projects Agency for Health (ARPA-H).

Bertagnolli will also head NCI efforts already underway to boost grant funding rates, diversify the cancer research workplace, and reduce higher death rates for Black people with cancer.

The White House recently nominated applied physicist Arati Prabhakar to fill another high-level science position, director of the White House Office of Science and Technology Policy (OSTP). But still vacant is the NIH director slot, which Francis Collins, acting science adviser to the president, left in December 2021. And the administration hasn’t yet selected the inaugural director of ARPA-H.

Correction, 22 July, 9 a.m.: This story has been updated to reflect that Francis Collins is acting science adviser to the president, not acting director of the White House Office of Science and Technology Policy.

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2022 Albert Lasker Basic Medical Research Award for Integrins—Mediators of Cell-Matrix and Cell-Cell Adhesion

Reporter: Aviva Lev-Ari, PhD, RN

 

The three recipients of 2022 Albert Lasker Basic Medical Research Award For discoveries concerning the integrins—key mediators of cell-matrix and cell-cell adhesion in physiology and disease are:

  • Richard O. Hynes, Massachusetts Institute of Technology
  • Erkki Ruoslahti, Sanford Burnham Prebys
  • Timothy A. Springer, Boston Children’s Hospital/Harvard Medical School

2022 Basic Award video

https://www.youtube.com/watch?v=4k60P3Pnh30

Acceptance remarks

Watch 3 Videos
 
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Figure 1A: Pairs that bond
Two protein chains, α and ß, compose the heterodimeric integrins that span the cell membrane. The portion outside affixes to molecules in the extracellular matrix (ECM) or on other cells. Adherence through integrins triggers cytoskeleton assembly and vice versa. Such events can also influence the behavior of other proteins inside the cell. The image shows the matrix-cell type of integrin; a second type mediates cell-cell interactions.
Illustration: Cassio Lynm / © Amino Creative

Figure 1B: Families that stick together
Integrin α and ß subunit each belong to a family of proteins with a shared evolutionary ancestor. Individual members of the α and ß families combine in different ways to create 24 mammalian heterodimers that physically associate with a variety of molecules. In the ECM, these binding partners include collagen, laminin, and other RGD-containing proteins such as fibronectin and fibrinogen; on cells, these partners include proteins such as ICAM-1, which dwells on the surface of white blood cells and cells that line blood vessels. The first integrin identified, the platelet receptor, promotes blood clotting. LFA-1 helps immune cells fight infections in numerous ways.
Illustration: Cassio Lynm / © Amino Creative

Figure 2: Fleeting attachments, profound effects
By fostering adherence between cells and the ECM or other cells, integrins play a key role in a tremendous number of essential physiological interactions.
Illustration: Cassio Lynm / © Amino Creative

Figures Source: 

https://laskerfoundation.org/winners/integrins-mediators-of-cell-matrix-cell-adhesion/

 

Selected Publications – Discovery of Integrins

Cell-Matrix Interactions

Ruoslahti, E., Vaheri. A., Kuusela, P., and Linder, E. (1973). Fibroblast surface antigen: a new serum protein. Biochim. BiophysActa. 322, 352-358.

Hynes, R.O. (1973). Alteration of cell-surface proteins by viral transformation and by proteolysis. Proc. Natl. Acad. Sci. USA70, 3170-3174.

Pierschbacher, M.D., and Ruoslahti, E. (1984). Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature309, 30-33.

Pytela, R., Pierschbacher, M.D., and Ruoslahti, E. (1985). A 125/115-kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin. Proc. Natl. Acad. Sci. USA. 82, 5766-5770.

Pytela, R., Pierschbacher, M.D., Ginsberg, M.H., Plow, E.F., and Ruoslahti, E. (1986). Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp-specific adhesion receptors. Science231, 1559-1562.

Tamkun, J.W., DeSimone, D.W., Fonda, D., Patel, R.S., Buck, C., Horwitz, A.F., and Hynes, R.O. (1986). Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell. 46, 271-282.

Hynes, R.O. (1987). Integrins: a family of cell surface receptors. Cell48, 549-554.

Ruoslahti, E. (1996). RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol. 12, 697-715.

Hynes, R.O. (2002). Integrins: bidirectional allosteric signaling machines. Cell. 110, 673-687.

Cell-Cell Interactions

Kurzinger, K., Reynolds, T., Germain, R.N., Davignon, D., Martz, E., and Springer, T.A. (1981). A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, quantitative expression, and structure. J. Immunol. 127, 596-600.

Sanchez-Madrid, F., Nagy, J., Robbins, E., Simon, P., and Springer, T.A. (1983). A human leukocyte differentiation antigen family with distinct alpha subunits and a common beta subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J. Exp. Med. 158, 1785-1789.

Thompson, W.S., Miller, L.J., Schmalstieg, F.C., Anderson, D.C., and Springer, T.A. (1984). Inherited deficiency of the Mac-1, LFA-1, p150,95 glycoprotein family and its molecular basis. J. Exp. Med. 160, 1901-1905.

Kishimoto, T.K., Lee, A., Roberts, T.M., and Springer, T.A. (1987). Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extra-cellular matrix receptor defines a novel supergene family. Cell. 48, 681-690.

Makgoba. M.W., Sanders, M.E., Luce, G.E.G., Dustin, M.L., Springer, T.A., Clark, E.A., Mannoni, P., and Shaw, S. (1988). ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells. Nature331, 86-88.

Staunton, D.E., Dustin, M.L., and Springer, T.A. (1989). Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature. 339, 61-65.

Springer, T.A. (1990). Adhesion receptors of the immune system. Nature. 346, 425-434.

Lawrence, M.B., and Springer, T.A. (1991). Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 65, 859-873.

Luo, B.-H., Carman, C.V., and Springer, T.A. (2007) Structural basis of integrin regulation and signaling. Annu. Rev. Immunol. 25, 619-647.

Li, J., Yan, J., and Springer, T.A. (2021). Low-affinity integrin states have faster ligand-binding kinetics than the high-affinity state. eLife. 10, 1-22. e73359. doi: 10.7554/eLife.73359.

SOURCE

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The Human Genome Gets Fully Sequenced: A Simplistic Take on Century Long Effort

 

Curator: Stephen J. Williams, PhD

Ever since the hard work by Rosalind Franklin to deduce structures of DNA and the coincidental work by Francis Crick and James Watson who modeled the basic building blocks of DNA, DNA has been considered as the basic unit of heredity and life, with the “Central Dogma” (DNA to RNA to Protein) at its core.  These were the discoveries in the early twentieth century, and helped drive the transformational shift of biological experimentation, from protein isolation and characterization to cloning protein-encoding genes to characterizing how the genes are expressed temporally, spatially, and contextually.

Rosalind Franklin, who’s crystolagraphic data led to determination of DNA structure. Shown as 1953 Time cover as Time person of the Year

Dr Francis Crick and James Watson in front of their model structure of DNA

 

 

 

 

 

 

 

 

 

Up to this point (1970s-mid 80s) , it was felt that genetic information was rather static, and the goal was still to understand and characterize protein structure and function while an understanding of the underlying genetic information was more important for efforts like linkage analysis of genetic defects and tools for the rapidly developing field of molecular biology.  But the development of the aforementioned molecular biology tools including DNA cloning, sequencing and synthesis, gave scientists the idea that a whole recording of the human genome might be possible and worth the effort.

How the Human Genome Project  Expanded our View of Genes Genetic Material and Biological Processes

 

 

From the Human Genome Project Information Archive

Source:  https://web.ornl.gov/sci/techresources/Human_Genome/project/hgp.shtml

History of the Human Genome Project

The Human Genome Project (HGP) refers to the international 13-year effort, formally begun in October 1990 and completed in 2003, to discover all the estimated 20,000-25,000 human genes and make them accessible for further biological study. Another project goal was to determine the complete sequence of the 3 billion DNA subunits (bases in the human genome). As part of the HGP, parallel studies were carried out on selected model organisms such as the bacterium E. coli and the mouse to help develop the technology and interpret human gene function. The DOE Human Genome Program and the NIH National Human Genome Research Institute (NHGRI) together sponsored the U.S. Human Genome Project.

 

Please see the following for goals, timelines, and funding for this project

 

History of the Project

It is interesting to note that multiple government legislation is credited for the funding of such a massive project including

Project Enabling Legislation

  • The Atomic Energy Act of 1946 (P.L. 79-585) provided the initial charter for a comprehensive program of research and development related to the utilization of fissionable and radioactive materials for medical, biological, and health purposes.
  • The Atomic Energy Act of 1954 (P.L. 83-706) further authorized the AEC “to conduct research on the biologic effects of ionizing radiation.”
  • The Energy Reorganization Act of 1974 (P.L. 93-438) provided that responsibilities of the Energy Research and Development Administration (ERDA) shall include “engaging in and supporting environmental, biomedical, physical, and safety research related to the development of energy resources and utilization technologies.”
  • The Federal Non-nuclear Energy Research and Development Act of 1974 (P.L. 93-577) authorized ERDA to conduct a comprehensive non-nuclear energy research, development, and demonstration program to include the environmental and social consequences of the various technologies.
  • The DOE Organization Act of 1977 (P.L. 95-91) mandated the Department “to assure incorporation of national environmental protection goals in the formulation and implementation of energy programs; and to advance the goal of restoring, protecting, and enhancing environmental quality, and assuring public health and safety,” and to conduct “a comprehensive program of research and development on the environmental effects of energy technology and program.”

It should also be emphasized that the project was not JUST funded through NIH but also Department of Energy

Project Sponsors

For a great read on Dr. Craig Ventnor with interviews with the scientist see Dr. Larry Bernstein’s excellent post The Human Genome Project

 

By 2003 we had gained much information about the structure of DNA, genes, exons, introns and allowed us to gain more insights into the diversity of genetic material and the underlying protein coding genes as well as many of the gene-expression regulatory elements.  However there was much uninvestigated material dispersed between genes, the then called “junk DNA” and, up to 2003 not much was known about the function of this ‘junk DNA’.  In addition there were two other problems:

  • The reference DNA used was actually from one person (Craig Ventor who was the lead initiator of the project)
  • Multiple gaps in the DNA sequence existed, and needed to be filled in

It is important to note that a tremendous amount of diversity of protein has been realized from both transcriptomic and proteomic studies.  Although about 20 to 25,000 coding genes exist the human proteome contains about 600,000 proteoforms (due to alternative splicing, posttranslational modifications etc.)

This expansion of the proteoform via alternate splicing into isoforms, gene duplication to paralogs has been shown to have major effects on, for example, cellular signaling pathways (1)

However just recently it has been reported that the FULL human genome has been sequenced and is complete and verified.  This was the focus of a recent issue in the journal Science.

Source: https://www.science.org/doi/10.1126/science.abj6987

Abstract

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion–base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.

 

The current human reference genome was released by the Genome Reference Consortium (GRC) in 2013 and most recently patched in 2019 (GRCh38.p13) (1). This reference traces its origin to the publicly funded Human Genome Project (2) and has been continually improved over the past two decades. Unlike the competing Celera effort (3) and most modern sequencing projects based on “shotgun” sequence assembly (4), the GRC assembly was constructed from sequenced bacterial artificial chromosomes (BACs) that were ordered and oriented along the human genome by means of radiation hybrid, genetic linkage, and fingerprint maps. However, limitations of BAC cloning led to an underrepresentation of repetitive sequences, and the opportunistic assembly of BACs derived from multiple individuals resulted in a mosaic of haplotypes. As a result, several GRC assembly gaps are unsolvable because of incompatible structural polymorphisms on their flanks, and many other repetitive and polymorphic regions were left unfinished or incorrectly assembled (5).

 

Fig. 1. Summary of the complete T2T-CHM13 human genome assembly.
(A) Ideogram of T2T-CHM13v1.1 assembly features. For each chromosome (chr), the following information is provided from bottom to top: gaps and issues in GRCh38 fixed by CHM13 overlaid with the density of genes exclusive to CHM13 in red; segmental duplications (SDs) (42) and centromeric satellites (CenSat) (30); and CHM13 ancestry predictions (EUR, European; SAS, South Asian; EAS, East Asian; AMR, ad-mixed American). Bottom scale is measured in Mbp. (B and C) Additional (nonsyntenic) bases in the CHM13 assembly relative to GRCh38 per chromosome, with the acrocentrics highlighted in black (B) and by sequence type (C). (Note that the CenSat and SD annotations overlap.) RepMask, RepeatMasker. (D) Total nongap bases in UCSC reference genome releases dating back to September 2000 (hg4) and ending with T2T-CHM13 in 2021. Mt/Y/Ns, mitochondria, chrY, and gaps.

Note in Figure 1D the exponential growth in genetic information.

Also very important is the ability to determine all the paralogs, isoforms, areas of potential epigenetic regulation, gene duplications, and transposable elements that exist within the human genome.

Analyses and resources

A number of companion studies were carried out to characterize the complete sequence of a human genome, including comprehensive analyses of centromeric satellites (30), segmental duplications (42), transcriptional (49) and epigenetic profiles (29), mobile elements (49), and variant calls (25). Up to 99% of the complete CHM13 genome can be confidently mapped with long-read sequencing, opening these regions of the genome to functional and variational analysis (23) (fig. S38 and table S14). We have produced a rich collection of annotations and omics datasets for CHM13—including RNA sequencing (RNA-seq) (30), Iso-seq (21), precision run-on sequencing (PRO-seq) (49), cleavage under targets and release using nuclease (CUT&RUN) (30), and ONT methylation (29) experiments—and have made these datasets available via a centralized University of California, Santa Cruz (UCSC), Assembly Hub genome browser (54).

 

To highlight the utility of these genetic and epigenetic resources mapped to a complete human genome, we provide the example of a segmentally duplicated region of the chromosome 4q subtelomere that is associated with facioscapulohumeral muscular dystrophy (FSHD) (55). This region includes FSHD region gene 1 (FRG1), FSHD region gene 2 (FRG2), and an intervening D4Z4 macrosatellite repeat containing the double homeobox 4 (DUX4) gene that has been implicated in the etiology of FSHD (56). Numerous duplications of this region throughout the genome have complicated past genetic analyses of FSHD.

The T2T-CHM13 assembly reveals 23 paralogs of FRG1 spread across all acrocentric chromosomes as well as chromosomes 9 and 20 (Fig. 5A). This gene appears to have undergone recent amplification in the great apes (57), and approximate locations of FRG1 paralogs were previously identified by FISH (58). However, only nine FRG1 paralogs are found in GRCh38, hampering sequence-based analysis.

Future of the human reference genome

The T2T-CHM13 assembly adds five full chromosome arms and more additional sequence than any genome reference release in the past 20 years (Fig. 1D). This 8% of the genome has not been overlooked because of a lack of importance but rather because of technological limitations. High-accuracy long-read sequencing has finally removed this technological barrier, enabling comprehensive studies of genomic variation across the entire human genome, which we expect to drive future discovery in human genomic health and disease. Such studies will necessarily require a complete and accurate human reference genome.

CHM13 lacks a Y chromosome, and homozygous Y-bearing CHMs are nonviable, so a different sample type will be required to complete this last remaining chromosome. However, given its haploid nature, it should be possible to assemble the Y chromosome from a male sample using the same methods described here and supplement the T2T-CHM13 reference assembly with a Y chromosome as needed.

Extending beyond the human reference genome, large-scale resequencing projects have revealed genomic variation across human populations. Our reanalyses of the 1KGP (25) and SGDP (42) datasets have already shown the advantages of T2T-CHM13, even for short-read analyses. However, these studies give only a glimpse of the extensive structural variation that lies within the most repetitive regions of the genome assembled here. Long-read resequencing studies are now needed to comprehensively survey polymorphic variation and reveal any phenotypic associations within these regions.

Although CHM13 represents a complete human haplotype, it does not capture the full diversity of human genetic variation. To address this bias, the Human Pangenome Reference Consortium (59) has joined with the T2T Consortium to build a collection of high-quality reference haplotypes from a diverse set of samples. Ideally, all genomes could be assembled at the quality achieved here, but automated T2T assembly of diploid genomes presents a difficult challenge that will require continued development. Until this goal is realized, and any human genome can be completely sequenced without error, the T2T-CHM13 assembly represents a more complete, representative, and accurate reference than GRCh38.

 

This paper was the focus of a Time article and their basis for making the lead authors part of their Time 100 people of the year.

From TIME

The Human Genome Is Finally Fully Sequenced

Source: https://time.com/6163452/human-genome-fully-sequenced/

 

The first human genome was mapped in 2001 as part of the Human Genome Project, but researchers knew it was neither complete nor completely accurate. Now, scientists have produced the most completely sequenced human genome to date, filling in gaps and correcting mistakes in the previous version.

The sequence is the most complete reference genome for any mammal so far. The findings from six new papers describing the genome, which were published in Science, should lead to a deeper understanding of human evolution and potentially reveal new targets for addressing a host of diseases.

A more precise human genome

“The Human Genome Project relied on DNA obtained through blood draws; that was the technology at the time,” says Adam Phillippy, head of genome informatics at the National Institutes of Health’s National Human Genome Research Institute (NHGRI) and senior author of one of the new papers. “The techniques at the time introduced errors and gaps that have persisted all of these years. It’s nice now to fill in those gaps and correct those mistakes.”

“We always knew there were parts missing, but I don’t think any of us appreciated how extensive they were, or how interesting,” says Michael Schatz, professor of computer science and biology at Johns Hopkins University and another senior author of the same paper.

The work is the result of the Telomere to Telomere consortium, which is supported by NHGRI and involves genetic and computational biology experts from dozens of institutes around the world. The group focused on filling in the 8% of the human genome that remained a genetic black hole from the first draft sequence. Since then, geneticists have been trying to add those missing portions bit by bit. The latest group of studies identifies about an entire chromosome’s worth of new sequences, representing 200 million more base pairs (the letters making up the genome) and 1,956 new genes.

 

NOTE: In 2001 many scientists postulated there were as much as 100,000 coding human genes however now we understand there are about 20,000 to 25,000 human coding genes.  This does not however take into account the multiple diversity obtained from alternate splicing, gene duplications, SNPs, and chromosomal rearrangements.

Scientists were also able to sequence the long stretches of DNA that contained repeated sequences, which genetic experts originally thought were similar to copying errors and dismissed as so-called “junk DNA”. These repeated sequences, however, may play roles in certain human diseases. “Just because a sequence is repetitive doesn’t mean it’s junk,” says Eichler. He points out that critical genes are embedded in these repeated regions—genes that contribute to machinery that creates proteins, genes that dictate how cells divide and split their DNA evenly into their two daughter cells, and human-specific genes that might distinguish the human species from our closest evolutionary relatives, the primates. In one of the papers, for example, researchers found that primates have different numbers of copies of these repeated regions than humans, and that they appear in different parts of the genome.

“These are some of the most important functions that are essential to live, and for making us human,” says Eichler. “Clearly, if you get rid of these genes, you don’t live. That’s not junk to me.”

Deciphering what these repeated sections mean, if anything, and how the sequences of previously unsequenced regions like the centromeres will translate to new therapies or better understanding of human disease, is just starting, says Deanna Church, a vice president at Inscripta, a genome engineering company who wrote a commentary accompanying the scientific articles. Having the full sequence of a human genome is different from decoding it; she notes that currently, of people with suspected genetic disorders whose genomes are sequenced, about half can be traced to specific changes in their DNA. That means much of what the human genome does still remains a mystery.

The investigators in the Telomere to Telomere Consortium made the Time 100 People of the Year.

Michael Schatz, Karen Miga, Evan Eichler, and Adam Phillippy

Illustration by Brian Lutz for Time (Source Photos: Will Kirk—Johns Hopkins University; Nick Gonzales—UC Santa Cruz; Patrick Kehoe; National Human Genome Research Institute)

BY JENNIFER DOUDNA

MAY 23, 2022 6:08 AM EDT

Ever since the draft of the human genome became available in 2001, there has been a nagging question about the genome’s “dark matter”—the parts of the map that were missed the first time through, and what they contained. Now, thanks to Adam Phillippy, Karen Miga, Evan Eichler, Michael Schatz, and the entire Telomere-to-Telomere Consortium (T2T) of scientists that they led, we can see the full map of the human genomic landscape—and there’s much to explore.

In the scientific community, there wasn’t a consensus that mapping these missing parts was necessary. Some in the field felt there was already plenty to do using the data in hand. In addition, overcoming the technical challenges to getting the missing information wasn’t possible until recently. But the more we learn about the genome, the more we understand that every piece of the puzzle is meaningful.

I admire the

T2T group’s willingness to grapple with the technical demands of this project and their persistence in expanding the genome map into uncharted territory. The complete human genome sequence is an invaluable resource that may provide new insights into the origin of diseases and how we can treat them. It also offers the most complete look yet at the genetic script underlying the very nature of who we are as human beings.

Doudna is a biochemist and winner of the 2020 Nobel Prize in Chemistry

Source: https://time.com/collection/100-most-influential-people-2022/6177818/evan-eichler-karen-miga-adam-phillippy-michael-schatz/

Other articles on the Human Genome Project and Junk DNA in this Open Access Scientific Journal Include:

 

International Award for Human Genome Project

 

Cracking the Genome – Inside the Race to Unlock Human DNA – quotes in newspapers

 

The Human Genome Project

 

Junk DNA and Breast Cancer

 

A Perspective on Personalized Medicine

 

 

 

 

 

 

 

Additional References

 

  1. P. Scalia, A. Giordano, C. Martini, S. J. Williams, Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer. Biomolecules 10, (Nov 30, 2020).

 

 

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Technion Prof. Emeritus Yoram Palti of the Faculty of Medicine will receive the 2022 Israel Prize in the Field of Entrepreneurship and Technological Innovation

Reporter: Aviva Lev-Ari, PhD, RN

Prof. Emeritus Yoram Palti of the Ruth and Bruce Rappaport Faculty of Medicine will receive the 2022 Israel Prize in the Field of Entrepreneurship and Technological Innovation. Prof. Palti developed groundbreaking cancer treatments that fight malignant brain tumors using electric pulses in a non-invasive manner.

SOURCE

https://mailchi.mp/technion/shaping-the-future-of-the-technion?e=d234e13770

An Interview and the milestones of the technology development is described in a Journal article

From the basement in Israel – to a global medical revolution: the innovative treatment of life-prolonging cancer

SOURCE

https://www.mako.co.il/news-n12_magazine/2021_q3/Article-2329c13a68afb71026.htm

 

Core Technology

The idea behind Tumor Treating Fields is simple yet ingenious: We harness basic physical principles using electric fields to disrupt cancer cell division.

Uri Weinberg,
Chief Science Officer

Tumor Treating Fields utilize the natural electrical properties of dividing cancer cells 

Cellular proteins such as tubulin and septin are strongly affected by Tumor Treating Fields because they are highly polar, containing both positive and negative charges. During cell division, tubulin and septin must position themselves in a particular way in order for the cell to divide. Tumor Treating Fields exert forces on tubulin and septin, preventing them from moving to their correct locations and disrupting cancer cell division.

Image Source: https://www.novocure.com/our-therapy/

Effect of Tumor Treating Fields

Image Source: https://www.novocure.com/our-therapy/

Novocure.com

We are striving to extend survival in some of the most aggressive forms of cancer.

In 2000, Yoram Palti, our founder and professor emeritus of physiology and biophysics at the Technion — Israel Institute of Technology, sought to leverage his expertise in biophysics to develop a new way to treat solid tumor cancers that would destroy tumor cells while sparing healthy tissue and avoiding many of the life-altering side effects of existing cancer therapies.

He set up a laboratory in his basement to explore the potential of electric fields as a treatment for solid tumors.

Professor Palti founded Novocure to provide patients with a new cancer treatment based on his hypothesis, since proven, that alternating electric fields, when applied at specific frequencies, can disrupt cancer cell division. This innovative treatment, Tumor Treating Fields, is a completely different approach to cancer therapy.

“Nobody understood what I was doing,” Professor Palti said of his early development of Tumor Treating Fields.

Palti’s initial research from his basement laboratory evolved to become Novocure – an international oncology company with more than 1,000 employees and operations in North America, Europe, the Middle East and Asia.

Our company began with a patient-forward approach that continues to drive our mission today. With more than 20 years of research and many significant milestones, we believe we are only beginning.

Read more …

SOURCE

https://www.novocure.com/about-us/

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2022 Lifetime Achievement Award Recipient: Marcus Feldman by the Society for the Study of Evolution

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 3/2/2022

We, at LPBI Group, the Founder, Aviva Lev-Ari, PhD, RN and the entire Team, External Scientific Relations, External Business Relations and LPBI India are very happy to congratulate our Board Member, Prof. Marcus W. Feldman for the prestigious award announced on 2/24/2022 by the Society for the Study of Evolution (SSE):

2022 Lifetime Achievement Award Recipient: Marcus Feldman

 

CONGRATUALTIONS !!!!!!

Aviva Lev-Ari, PhD, RN

Director & Founder

https://lnkd.in/eEyn69r

Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston, MA

Editor-in-Chief

http://pharmaceuticalintelligence.com 

e-Mail: avivalev-ari@alum.berkeley.edu

(M) 617-775-0451

 

2022 Lifetime Achievement Award Recipient: Marcus Feldman

Contributed by kjm34 on Feb 24, 2022 – 02:12 PM

The words Marcus Feldman, 2022 Society for the Study of Evolution Lifetime Achievement Award in black text on a light green background next to a photo for Dr. Feldman.

SSE Council is pleased to announce the recipient of the 2022 SSE Lifetime Achievement AwardDr. Marcus Feldman. 

Dr. Feldman is the Burnet C. and Mildred Finley Wohlford Professor of Biology, founder and director of the Morrison Institute for Population and Resource Studies, and co-director of the Center for Computational, Evolutionary and Human Genomics at Stanford University. His innovative research has contributed to our understanding of the evolution of recombination and sex, human population genetics, niche construction, and evolutionary theory. With Dr. Luca Cavalli-Sforza, Dr. Feldman also developed a new field termed cultural evolution, which studies how genetic and cultural variation can interact and affect one another. Over the course of his career, he has mentored numerous trainees, from high school students to postdocs, and was awarded the Allan V. Cox Medal for Fostering Undergraduate Research at Stanford and  the Stanford Biosciences Excellence in Mentoring and Service Award. In 1970, he co-founded the journal Theoretical Population Biology. He was also the Editor of The American Naturalist from 1984 to 1990. Dr. Feldman was named the Dan David Laureate in Evolution in 2011, and received the Motoo Kimura Prize in Human Evolution in 2016.

SOURCES

http://www.evolutionsociety.org/news/view/2022 Lifetime Achievement Award Recipient: Marcus Feldman by the Society for the Study of Evolution

http://www.evolutionsociety.org/news/display/2022/2/24/2022-lifetime-achievement-award-recipient-marcus-feldman/

Podcast with Prof. Feldman by Gail Thornton

  • Podcast with Prof. Marcus W. Feldman, PhD, Biology Department, Stanford University, Interview by Gail S. Thornton, PhDc

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The Nobel Prize in Chemistry 2021

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED ON 12/18/2021

12/8/2021, Stockholm, Sweden

6 October 2021

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2021

to

Benjamin List
Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany

David W.C. MacMillan
Princeton University, USA

“for the development of asymmetric organocatalysis”

Meet UC’s 2021 Nobelists

Three UC-affiliated scientists have won Nobel Prizes this year: UCSF professor David Julius, UCLA alum Ardem Patapoutian and UC Irvine alum David W.C. MacMillan.

SOURCE

UC’s new Nobelists
UC San Francisco, UCLA and UC Irvine
Three UC-affiliated scientists were awarded Nobel Prizes this week. UC San Francisco professor David Julius shared the Nobel Prize in physiology or medicine with UCLA alum Ardem Patapoutian. UC Irvine alum David W.C. MacMillan won in chemistry. 

From: University of California <webeditor@ucop.edu>
Reply-To: University of California <webeditor@ucop.edu>
Date: Friday, October 8, 2021 at 1:02 PM
To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu>
Subject: 3 UC Nobel Prize winners!

IMAGE SOURCE:
Chemistry Nobel Prize Honors Technique for Building Molecules. Benjamin List and David MacMillan received the 2021 Nobel Prize in Chemistry for their development of asymmetrical organocatalysis. https://www.quantamagazine.org/chemistry-nobel-prize-honors-technique-for-building-molecules-20211006/

An ingenious tool for building molecules

Building molecules is a difficult art. Benjamin List and David MacMillan are awarded the Nobel Prize in Chemistry 2021 for their development of a precise new tool for molecular construction: organocatalysis. This has had a great impact on pharmaceutical research, and has made chemistry greener.

Many research areas and industries are dependent on chemists’ ability to construct molecules that can form elastic and durable materials, store energy in batteries or inhibit the progression of diseases. This work requires catalysts, which are substances that control and accelerate chemical reactions, without becoming part of the final product. For example, catalysts in cars transform toxic substances in exhaust fumes to harmless molecules. Our bodies also contain thousands of catalysts in the form of enzymes, which chisel out the molecules necessary for life.

Catalysts are thus fundamental tools for chemists, but researchers long believed that there were, in principle, just two types of catalysts available: metals and enzymes. Benjamin List and David MacMillan are awarded the Nobel Prize in Chemistry 2021 because in 2000 they, independent of each other, developed a third type of catalysis. It is called asymmetric organocatalysis and builds upon small organic molecules.

“This concept for catalysis is as simple as it is ingenious, and the fact is that many people have wondered why we didn’t think of it earlier,” says Johan Åqvist, who is chair of the Nobel Committee for Chemistry.

Organic catalysts have a stable framework of carbon atoms, to which more active chemical groups can attach. These often contain common elements such as oxygen, nitrogen, sulphur or phosphorus. This means that these catalysts are both environmentally friendly and cheap to produce.

The rapid expansion in the use of organic catalysts is primarily due to their ability to drive asymmetric catalysis. When molecules are being built, situations often occur where two different molecules can form, which – just like our hands – are each other’s mirror image. Chemists will often only want one of these, particularly when producing pharmaceuticals.

Organocatalysis has developed at an astounding speed since 2000. Benjamin List and David MacMillan remain leaders in the field, and have shown that organic catalysts can be used to drive multitudes of chemical reactions. Using these reactions, researchers can now more efficiently construct anything from new pharmaceuticals to molecules that can capture light in solar cells. In this way, organocatalysts are bringing the greatest benefit to humankind.

Benjamin List, born 1968 in Frankfurt, Germany. Ph.D. 1997 from Goethe University Frankfurt, Germany. Director of the Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany.

David W.C. MacMillan, born 1968 in Bellshill, UK. Ph.D. 1996 from University of California, Irvine, USA. Professor at Princeton University, USA.

Prize amount: 10 million Swedish kronor, to be shared equally between the Laureates.
Further information: http://www.kva.se and http://www.nobelprize.org

SOURCE

https://www.nobelprize.org/prizes/chemistry/2021/press-release/

Scientific Background: Enamine and iminium ion-mediated organocatalysis (pdf)

Chemistry Nobel Prize Honors Technique for Building Molecules

by Jordana Cepelewicz

https://www.quantamagazine.org/chemistry-nobel-prize-honors-technique-for-building-molecules-20211006/

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The Nobel Prize in Physiology or Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian “for their discoveries of receptors for temperature and touch.”

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 12/18/2021

Nobel Prize Lecture in Stockholm, Sweden, 12/7/2021

UPDATED on 10/14/2021

49th (2019) – Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research

for their remarkable contributions to our understanding of the sensations of temperature, pain and touch

David Julius – 49th (2019) – Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research

for their remarkable contributions to our understanding of the sensations of temperature, pain and touch


(2021 Nobel Prize)
Morris Herzstein Chair in Molecular Biology and Medicine
Professor and Chair, Department of Physiology
School of Medicine
The University of California, San Francisco
San Francisco, CA USA

Ardem Patapoutian – 49th (2019) – Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research for their remarkable contributions to our understanding of the sensations of temperature, pain and touch


(2021 Nobel Prize)

Investigator, Howard Hughes Medical Institute
Professor, Department of Neuroscience
The Scripps Research Institute
La Jolla, CA USA

Press release: The Nobel Prize in Physiology or Medicine 2021. NobelPrize.org. Nobel Prize Outreach AB 2021. Mon. 4 Oct 2021. <https://www.nobelprize.org/prizes/medicine/2021/press-release/>

David Julius was born in 1955 in New York, USA. He received a Ph.D. in 1984 from University of California, Berkeley and was a postdoctoral fellow at Columbia University, in New York. David Julius was recruited to the University of California, San Francisco in 1989 where he is now Professor.

Ardem Patapoutian was born in 1967 in Beirut, Lebanon. In his youth, he moved from a war-torn Beirut to Los Angeles, USA and received a Ph.D. in 1996 from California Institute of Technology, Pasadena, USA. He was a postdoctoral fellow at the University of California, San Francisco. Since 2000, he is a scientist at Scripps Research, La Jolla, California where he is now Professor. He is a Howard Hughes Medical Institute Investigator since 2014.

Meet UC’s 2021 Nobelists

Three UC-affiliated scientists have won Nobel Prizes this year: UCSF professor David Julius, UCLA alum Ardem Patapoutian and UC Irvine alum David W.C. MacMillan.

SOURCE

UC’s new Nobelists
UC San Francisco, UCLA and UC Irvine
Three UC-affiliated scientists were awarded Nobel Prizes this week. UC San Francisco professor David Julius shared the Nobel Prize in physiology or medicine with UCLA alum Ardem Patapoutian. UC Irvine alum David W.C. MacMillan won in chemistry. 

From: University of California <webeditor@ucop.edu>
Reply-To: University of California <webeditor@ucop.edu>
Date: Friday, October 8, 2021 at 1:02 PM
To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu>
Subject: 3 UC Nobel Prize winners!

Key publications

Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997:389:816-824.

Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998:21:531-543.

Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000:288:306-313

McKemy DD, Neuhausser WM, Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 2002:416:52-58

Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A. A TRP channel that senses cold stimuli and menthol. Cell 2002:108:705-715

Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 2010:330: 55-60

Ranade SS, Woo SH, Dubin AE, Moshourab RA, Wetzel C, Petrus M, Mathur J, Bégay V, Coste B, Mainquist J, Wilson AJ, Francisco AG, Reddy K, Qiu Z, Wood JN, Lewin GR, Patapoutian A. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 2014:516:121-125

Discoveries by this year's Nobel Prize laureates
Figure 4 The seminal discoveries by this year’s Nobel Prize laureates have explained how heat, cold and touch can initiate signals in our nervous system. The identified ion channels are important for many physiological processes and disease conditions.

IMAGE SOURCE: https://www.nobelprize.org/prizes/medicine/2021/press-release/


The science heats up!

In the latter part of the 1990’s, David Julius at the University of California, San Francisco, USA, saw the possibility for major advances by analyzing how the chemical compound capsaicin causes the burning sensation we feel when we come into contact with chili peppers. Capsaicin was already known to activate nerve cells causing pain sensations, but how this chemical actually exerted this function was an unsolved riddle. Julius and his co-workers created a library of millions of DNA fragments corresponding to genes that are expressed in the sensory neurons which can react to pain, heat, and touch. Julius and colleagues hypothesized that the library would include a DNA fragment encoding the protein capable of reacting to capsaicin. They expressed individual genes from this collection in cultured cells that normally do not react to capsaicin. After a laborious search, a single gene was identified that was able to make cells capsaicin sensitive (Figure 2). The gene for capsaicin sensing had been found! Further experiments revealed that the identified gene encoded a novel ion channel protein and this newly discovered capsaicin receptor was later named TRPV1. When Julius investigated the protein’s ability to respond to heat, he realized that he had discovered a heat-sensing receptor that is activated at temperatures perceived as painful (Figure 2).

David Julius' work
Figure 2 David Julius used capsaicin from chili peppers to identify TRPV1, an ion channel activated by painful heat. Additional related ion channels were identified and we now understand how different temperatures can induce electrical signals in the nervous system.

The discovery of TRPV1 was a major breakthrough leading the way to the unravelling of additional temperature-sensing receptors. Independently of one another, both David Julius and Ardem Patapoutian used the chemical substance menthol to identify TRPM8, a receptor that was shown to be activated by cold. Additional ion channels related to TRPV1 and TRPM8 were identified and found to be activated by a range of different temperatures. Many laboratories pursued research programs to investigate the roles of these channels in thermal sensation by using genetically manipulated mice that lacked these newly discovered genes. David Julius’ discovery of TRPV1 was the breakthrough that allowed us to understand how differences in temperature can induce electrical signals in the nervous system.

SOURCE

https://www.nobelprize.org/prizes/medicine/2021/press-release/

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The NIH-funded adjuvant improves the efficacy of India’s COVID-19 vaccine.

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), Part of National Institute of Health (NIH) said,

Ending a global pandemic demands a global response. I am thrilled that a novel vaccine adjuvant developed in the United States with NIAID support is now included in an effective COVID-19 vaccine that is available to individuals in India.”

Adjuvants are components that are created as part of a vaccine to improve immune responses and increase the efficiency of the vaccine. COVAXIN was developed and is manufactured in India, which is currently experiencing a terrible health catastrophe as a result of COVID-19. An adjuvant designed with NIH funding has contributed to the success of the extremely effective COVAXIN-COVID-19 vaccine, which has been administered to about 25 million individuals in India and internationally.

Alhydroxiquim-II is the adjuvant utilized in COVAXIN, was discovered and validated in the laboratory by the biotech company ViroVax LLC of Lawrence, Kansas, with funding provided solely by the NIAID Adjuvant Development Program. The adjuvant is formed of a small molecule that is uniquely bonded to Alhydrogel, often known as alum and the most regularly used adjuvant in human vaccines. Alhydroxiquim-II enters lymph nodes, where it detaches from alum and triggers two cellular receptors. TLR7 and TLR8 receptors are essential in the immunological response to viruses. Alhydroxiquim-II is the first adjuvant to activate TLR7 and TLR8 in an approved vaccine against an infectious disease. Additionally, the alum in Alhydroxiquim-II activates the immune system to look for an infiltrating pathogen.

Although molecules that activate TLR receptors strongly stimulate the immune system, the adverse effects of Alhydroxiquim-II are modest. This is due to the fact that after COVAXIN is injected, the adjuvant travels directly to adjacent lymph nodes, which contain white blood cells that are crucial in recognizing pathogens and combating infections. As a result, just a minimal amount of Alhydroxiquim-II is required in each vaccination dosage, and the adjuvant does not circulate throughout the body, avoiding more widespread inflammation and unwanted side effects.

This scanning electron microscope image shows SARS-CoV-2 (round gold particles) emerging from the surface of a cell cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. Image Source: NIAID

COVAXIN is made up of a crippled version of SARS-CoV-2 that cannot replicate but yet encourages the immune system to produce antibodies against the virus. The NIH stated that COVAXIN is “safe and well tolerated,” citing the results of a phase 2 clinical investigation. COVAXIN safety results from a Phase 3 trial with 25,800 participants in India will be released later this year. Meanwhile, unpublished interim data from the Phase 3 trial show that the vaccine is 78% effective against symptomatic sickness, 100% effective against severe COVID-19, including hospitalization, and 70% effective against asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19. Two tests of blood serum from persons who had received COVAXIN suggest that the vaccine creates antibodies that efficiently neutralize the SARS-CoV-2 B.1.1.7 (Alpha) and B.1.617 (Delta) variants (1) and (2), which were originally identified in the United Kingdom and India, respectively.

Since 2009, the NIAID Adjuvant Program has supported the research of ViroVax’s founder and CEO, Sunil David, M.D., Ph.D. His research has focused on the emergence of new compounds that activate innate immune receptors and their application as vaccination adjuvants.

Dr. David’s engagement with Bharat Biotech International Ltd. of Hyderabad, which manufactures COVAXIN, began during a 2019 meeting in India organized by the NIAID Office of Global Research under the auspices of the NIAID’s Indo-US Vaccine Action Program. Five NIAID-funded adjuvant investigators, including Dr. David, two representatives of the NIAID Division of Allergy, Immunology, and Transplantation, and the NIAID India representative, visited 4 top biotechnology companies to learn about their work and discuss future collaborations. The delegation also attended a consultation in New Delhi, which was co-organized by the NIAID and India’s Department of Biotechnology and hosted by the National Institute of Immunology.

Among the scientific collaborations spawned by these endeavors was a licensing deal between Bharat Biotech and Dr. David to use Alhydroxiquim-II in their candidate vaccines. During the COVID-19 outbreak, this license was expanded to cover COVAXIN, which has Emergency Use Authorization in India and more than a dozen additional countries. COVAXIN was developed by Bharat Biotech in partnership with the Indian Council of Medical Research’s National Institute of Virology. The company conducted thorough safety research on Alhydroxiquim-II and undertook the arduous process of scaling up production of the adjuvant in accordance with Good Manufacturing Practice standards. Bharat Biotech aims to generate 700 million doses of COVAXIN by the end of 2021.

NIAID conducts and supports research at the National Institutes of Health, across the United States, and across the world to better understand the causes of infectious and immune-mediated diseases and to develop better methods of preventing, detecting, and treating these illnesses. The NIAID website contains news releases, info sheets, and other NIAID-related materials.

Main Source:

https://www.miragenews.com/adjuvant-developed-with-nih-funding-enhances-587090/

References

  1. https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciab411/6271524?redirectedFrom=fulltext
  2. https://academic.oup.com/jtm/article/28/4/taab051/6193609

Other Related Articles published in this Open Access Online Scientific Journal include the following:

Comparing COVID-19 Vaccine Schedule Combinations, or “Com-COV” – First-of-its-Kind Study will explore the Impact of using eight different Combinations of Doses and Dosing Intervals for Different COVID-19 Vaccines

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/08/comparing-covid-19-vaccine-schedule-combinations-or-com-cov-first-of-its-kind-study-will-explore-the-impact-of-using-eight-different-combinations-of-doses-and-dosing-intervals-for-diffe/

Thriving Vaccines and Research: Weizmann Institute Coronavirus Research Development

Reporter:Amandeep Kaur, B.Sc., M.Sc.

https://pharmaceuticalintelligence.com/2021/05/04/thriving-vaccines-and-research-weizmann-coronavirus-research-development/

National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/07/19/national-public-radio-interview-with-dr-anthony-fauci-on-his-optimism-on-a-covid-19-vaccine-by-early-2021/

Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/04/10/cryo-em-disclosed-how-the-d614g-mutation-changes-sars-cov-2-spike-protein-structure/

Updates on the Oxford, AstraZeneca COVID-19 Vaccine

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/06/16/updates-on-the-oxford-astrazeneca-covid-19-vaccine/

Read Full Post »

LIVE – 50th Annual Lewis S. Rosenstiel Award to Katalin Karikó and Drew Weissman for work on messenger RNA, modification of Nucleic Acids applied in the development of COVID-19 Vaccines

Reporter & Real Time Coverage on 2/8/2021

 

50th Annual Lewis S. Rosenstiel Award to Katalin Karikó and Drew Weissman for work on messenger RNA, modification of Nucleic Acids applied in the development of COVID-19 Vaccines

Rosenstiel Award given to pioneering scientists behind COVID-19 vaccines

This year’s prize for distinguished work in basic medical research was awarded to Katalin Karikó and Drew Weissman for work on messenger RNA.

Katalin Karikó and Drew WeissmanCourtesy Karikó/University of Pennsylvania Katalin Karikó and Drew Weissman

Brandeis University and the Rosenstiel Foundation are pleased to award the 50th annual Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research to Katalin Karikó and Drew Weissman ’81, MA ’81, P’15, for their groundbreaking work in the modification of nucleic acids to develop RNA therapeutics and vaccines.

Karikó, senior vice president at BioNTech RNA Pharmaceuticals, and Weissman, a professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, pioneered much of the science underlying two of the COVID-19 vaccines now being given to tens of millions of people across the globe.

Rosenstiel Medal

For those of you who would like to share the recording of this event with others, or those of you who were not able to attend the web event, the recording of the program can be found here: 

https://ensemble.brandeis.edu/Watch/Aj7x3G8L

SOURCE

From: Ron Liebowitz <president@brandeis.edu>

Date: Thursday, February 11, 2021 at 5:48 PM

The Rosenstiel Award

By engineering a modified version of the messenger RNA (mRNA) inside human cells and then developing a system to deliver it to its target, the two researchers laid the groundwork for the vaccines brought to fruition by Pfizer/BioNTech and Moderna.

“This award celebrates how basic research in molecular biology can be the foundation for applications that can affect the lives of us all,” said James Haber, the Abraham and Etta Goodman Professor of Biology and director of the Rosenstiel Basic Medical Sciences Research Center.

“Through their painstaking research into mRNA – and persistence despite setbacks – Weissman and Karikó laid the groundwork for vaccines that will save countless lives.”

Peter Gruber Endowed Chair in Neuroscience and 2017 winner of the Nobel Prize in Physiology or Medicine Michael Rosbash said:

“Among the few positive consequences of the current pandemic are the successful efforts made worldwide to generate effective vaccines. The most creative of these rely on the new messenger RNA technology pioneered by Kariko and Weissman. This is a great story where individual initiative in basic science has ended up having a remarkable real-world impact.”

The Rosenstiel Award has had a distinguished record of identifying and honoring scientists who subsequently have been honored with the Lasker and Nobel Prizes. Thirty-six of 93 Rosenstiel Award winners have subsequently been awarded the Nobel Prize in Medicine or Physiology or in Chemistry.

A full list of awardees can be found on the award’s website.

The award will be presented on February 8 at 12 p.m. via webinar.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and Derrick Rossi, co-founder of Moderna, will present congratulatory remarks.

Karikó and Weissman began working together over 20 years ago when both were at U Penn.

At the time, many scientists didn’t believe mRNA, which transport instructions from DNA to the ribosomes for the production of proteins, could be the basis for a vaccine. In experiments, injecting mRNA into mice caused deadly inflammation.

But Karikó and Weissman pressed on, discovering a method of altering mRNA that enabled it to enter cells without triggering the body’s immune system. They did this by tweaking one of the four nucleosides that are the building blocks of mRNA.

Several years later, Karikó and Weissman devised a method of packaging mRNA inside a lipid nanoparticle — a small bubble of oil — so that the molecule didn’t fall apart as it traveled through the body.

“We basically tested every possible delivery system and found this was the best,” Weissman recently told BrandeisNOW.

The COVID-19 mRNA vaccines work by spurring human cells to produce the spike-shaped protein found on SARS-CoV-2, the virus that causes the illness, and triggering the immune system to produce protective antibodies.

In general, mRNA vaccines have the advantage of being cheaper to produce than traditional vaccines for chickenpox, polio, flu or rabies. It’s also hoped they can be adapted to treat other infectious diseases such as genital herpes (which is caused by the herpes simplex virus), influenza, Zika and HIV.

“The COVID-19 vaccine breakthrough is a great example of how basic science innovations, such as the RNA technology pioneered by Weissman and Karikó, can have an enormous impact on advances in the biomedical sciences,” said biochemist Carol Fierke, the university’s new provost and executive vice president.

In addition to her post at BioNTech, Karikó is an adjunct associate professor at the Perelman School of Medicine at the University of Pennsylvania. Weissman is also director of vaccine research at the Perelman school’s division of infectious diseases.

LAST PAST 5 Years Recipients

Past Winners

49th (2019)

for their remarkable contributions to our understanding of the sensations of temperature, pain and touch

David Julius
Morris Herzstein Chair in Molecular Biology and Medicine
Professor and Chair, Department of Physiology
School of Medicine
The University of California, San Francisco
San Francisco, CA USA

Ardem Patapoutian
Investigator, Howard Hughes Medical Institute
Professor, Department of Neuroscience
The Scripps Research Institute
La Jolla, CA USA

48th (2018)

for his fundamental and far-reaching studies of protein structure using X-ray crystallography

Steven C. Harrison
Investigator, Howard Hughes Medical Institute
Giovanni Armenise-Harvard Professor of Basic Medical Sciences
Harvard Medical School
Chief, Division of Molecular Medicine
Boston Children’s Hospital
Boston, MA USA

VIDEO: 48TH AWARD LECTURE

47th (2017)

for her elucidation of the protection of telomeres and the maintenance of genome stability

Titia de Lange
Leon Hess Professor
American Cancer Society Research Professor
Head, Laboratory of Cell Biology and Genetics
Director, Anderson Center for Cancer Research
The Rockefeller University
New York, NY USA

VIDEO: 47TH AWARD LECTURE

46th (2016)

in recognition of her pioneering work on the mechanisms of protein folding and the severe consequences of protein misfolding that are manifest in disease

Susan Lindquist (1949-2016)
Professor
 of Biology
Investigator, Howard Hughes Medical Institute
Member, Whitehead Institute
Massachusetts Institute of Technology
Cambridge, MA USA

VIDEO: 46TH AWARD LECTURES

45th (2015)

in recognition of his pioneering discoveries of molecular pathways and biological functions of protein degradation by autophagy

Yoshinori Ohsumi
(2016 Nobel Prize)
Professor
Frontier Research Center
Tokyo Institute of Technology
Tokyo, Japan

SOURCE

https://www.brandeis.edu/now/2021/january/rosenstiel-covid-vaccine.html

https://www.brandeis.edu/rosenstiel/rosenstiel-award/past.html

From: Brandeis Special Events <specialevents@brandeis.edu>

Reply-To: <specialevents@brandeis.edu>

Date: Friday, January 22, 2021 at 2:18 PM

To: “Aviva Lev-Ari, PhD, RN” <AvivaLev-Ari@alum.berkeley.edu>

Subject: Brandeis University: 50th Annual Lewis S. Rosenstiel Award Ceremony

LIVE

Prof. James Haber

  • synthetic modified mRNA to produce the Spike protein
  • bypassing messenger RNA to curtail the efficacy of the infective power of the messenger

Dr. Derrick Rossi

  • 2010 Founded Moderna
  • He is the CEO of Convelo Therapeutics.
  • DNA instructions of life are initiated
  • instructions for protein made in cytoplasm
  • intermediary mRNA (single structured) from DNA (double structured) transmitted to RNA
  • Why mRNA are not used in most labs? vs DNA and proteins
  • Gene therapy is DNA therapy
  • mRNA – is neglected = cellular reprogramming – therapeutic potential 2012 Nobel Prize by Japanese
  • mRNA immediately degrades
  • mRNA  is intrinsically immunogenic
  • mRNA reside in nucleosides, paper in 2005, mRNA therapeutics potential discovery
  • UPenn licensed the discovery to a company
  • Most future vaccines will be mRNA
  • DNA and Recombinant DNA for therapeutics
  • Katalin Karikó and Drew Weissman – Lead contributors

Katalin Karikó, 1989 joined UPenn – Development of mRNA for Therapy

Sr. VP BioNtech Therapeutics

  • mRNA get the message to Ribosome translate to protein
  • plasmid DNA – SP6 PNA polymerase 1984 – transcription/capping
  • Human interferon IFN CDS
  • injecting mRNA to mice 1990 – cap analog va enzymatic cap
  • mRNA work in vivo – 1990 – Gene Therapy and gene delivery
  • mRNA for therapeutic – synthesis of mRNA and evaluating in mammalian cells
  • DNA isolate cDNA synthesis amplifying DNA then DNA Seq
  • 1989 Taq DNA polymerase
  • Transfection – Lipofectin – 1987
  • IVT – evaluating gag mRNA in human dendritic cells – immune response detected
  • immunogenecity – mRNA
  • Dendritic – RNA transfection monocyte-derived human DCs ..inflammation response
  • tRNA – is enriched
  • modifying enzymes were unknown
  • incorporation of modified nucleotides into RNA by in vitro transcription
  • measuring inflammatory response
  • modified URIDINE-containing mRNA in Non-immunogenic
  • it Dimerize TLR7 & TLR*
  • Superior translation of lipofectin-derived pseudouridine-modified mRNA
  • Pseudouridine-containing mEPO mRNA delivery –
  • modified mRNA – HCT increases due to EPO –
  • Optimizing IVT mRNA
  • highly translatable mRNA – All
  • mRNA – new class of medicine – highly translatable
  • mRNA-loaded nanoparticle – human heart
  • cytokine response inflammatory
  • mRNA monoclonal antibodies

Dr. Faucci

  • mRNA based vaccine BioNtech in Germany and Moderna in Cambridge, MA
  • Basic research led to development of the Vaccine for the Pandemic

Dr. Drew Weissman

  • Nucleoside-modified mRNA SAR-COV-2
  • Viral Vectored RNA platform
  1. Inactivated or live virus
  2. viral vector
  3. DNA
  4. mRNA
  5. protein subunits
  • CORONAVIRUS: Respiratory, GI in human and animals
  • 2002 – SARS Bat -> civets ->human
  • Human to Human was not effective but 10% mortality
  • MERS-COv: Camel ->> Human
  • PAN coronavirus vaccine;
  • Discovery of mRNA: DNA transcription RNA translation protein
  • Nucleoside-modified
  • Benefits of RNA-based vaccines: can’t change DNA RNA is NON replication vector- short-lived controllable
  • Pfizer/BioNTech and Moderna vaccine works:
  1. Inject vaccine – induce potent immune response – Uptake spike protein produced immune response trigered antibody T and B cell mount response
  2. Vaccine efficacy 27 days after 2nd dose 94.8%
  • 5 in a million – anafilactic response
  • NO CHANGE to DNA by the mRNA vaccine

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Allon Klein, Harvard Medical School, and Aviv Regev, Genentech, Recipients of National Academy of Sciences James Prize in Science and Technology Integration 2021 Award

Reporter: Aviva Lev-Ari, PhD, RN

 

The National Academy of Sciences will award the inaugural James Prize in Science and Technology Integration to Allon Klein, Harvard Medical School, and Aviv Regev, Genentech Research and Early Development, the Broad Institute of MIT and Harvard, and Howard Hughes Medical Institute. They are receiving the $50,000 prize for “their concurrent development of now widely adopted massively parallel single-cell genomics to interrogate the gene expression profiles that define, at the level of individual cells, the distinct cell types in metazoan tissues, their developmental trajectories, and disease states, which integrated tools from molecular biology, engineering, statistics, and computer science.” The James Prize honors outstanding contributions made by researchers who are able to adopt or adapt information or techniques from outside their fields, integrating knowledge from two or more disciplines (e.g., engineering, mathematics, physics, chemistry, biology, biomedicine, geosciences, astronomy, or computational sciences) to solve a major contemporary challenge not addressable from a single disciplinary perspective.

 

Klein is recognized for innovating high-throughput experimental and mathematical approaches to analyze single-cell transcriptomes at an unprecedented level of detail and discover how cell fate is decided in metazoan tissues. His work combines statistics and physics with molecular biology. He has mapped differentiation hierarchies, identified transitional developmental states to predict features of fate control, and discovered new cell types and regenerative programs.

Regev is credited with forging new ways to unite the disciplines of biology, computational science, and engineering as a pioneer in the field of single-cell biology, including developing some of its core experimental and analysis tools, and their application to discover cell types, states, programs,  environmental responses, development, tissue locations, and regulatory circuits, and deploying these to assemble cellular atlases of the human body that illuminate mechanisms of disease with remarkable fidelity.

The prize, made possible through a generous donation from Robert “Bob” James, will be presented to Klein and Regev virtually during the National Academy of Sciences’ 158th annual meeting.

 
Awards News

 

» Stay tuned! The 2021 NAS Awards recipients will be announced on January 21 with the NAS Public Welfare Medal announced on January 25.
» In a recent episode of the podcast Clear+Vivid, hosted by 2016 Public Welfare Medalist Alan Alda, Marcia McNutt discusses her framework for delivering science in a crisis and how the National Academies are advising the nation during the COVID-19 pandemic. Click here to listen.

SOURCE

From: NAS Awards Program <awards@nas.edu>

Reply-To: NAS Awards Program <awards@nas.edu>

Date: Tuesday, January 19, 2021 at 11:04 AM

To: “Aviva Lev-Ari, PhD, RN” <AvivaLev-Ari@alum.berkeley.edu>

Subject: Inaugural James Prize in Science and Technology Integration Recipients Announced

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