Daily Archives: March 23, 2021

The history of genetics dates from the classical era with contributions by Pythagoras, Hippocrates, Aristotle, Epicurus, and others. Modern genetics began with the work of the Augustinian friar Gregor Johann Mendel. His work on pea plants, published in 1866, established the theory of Mendelian inheritance.

The year 1900 marked the "rediscovery of Mendel" by Hugo de Vries, Carl Correns and Erich von Tschermak, and by 1915 the basic principles of Mendelian genetics had been studied in a wide variety of organisms most notably the fruit fly Drosophila melanogaster. Led by Thomas Hunt Morgan and his fellow "drosophilists", geneticists developed the Mendelian model, which was widely accepted by 1925. Alongside experimental work, mathematicians developed the statistical framework of population genetics, bringing genetic explanations into the study of evolution.

With the basic patterns of genetic inheritance established, many biologists turned to investigations of the physical nature of the gene. In the 1940s and early 1950s, experiments pointed to DNA as the portion of chromosomes (and perhaps other nucleoproteins) that held genes. A focus on new model organisms such as viruses and bacteria, along with the discovery of the double helical structure of DNA in 1953, marked the transition to the era of molecular genetics.

In the following years, chemists developed techniques for sequencing both nucleic acids and proteins, while many others worked out the relationship between these two forms of biological molecules and discovered the genetic code. The regulation of gene expression became a central issue in the 1960s; by the 1970s gene expression could be controlled and manipulated through genetic engineering. In the last decades of the 20th century, many biologists focused on large-scale genetics projects, such as sequencing entire genomes.

The most influential early theories of heredity were that of Hippocrates and Aristotle. Hippocrates' theory (possibly based on the teachings of Anaxagoras) was similar to Darwin's later ideas on pangenesis, involving heredity material that collects from throughout the body. Aristotle suggested instead that the (nonphysical) form-giving principle of an organism was transmitted through semen (which he considered to be a purified form of blood) and the mother's menstrual blood, which interacted in the womb to direct an organism's early development.[1] For both Hippocrates and Aristotleand nearly all Western scholars through to the late 19th centurythe inheritance of acquired characters was a supposedly well-established fact that any adequate theory of heredity had to explain. At the same time, individual species were taken to have a fixed essence; such inherited changes were merely superficial.[2] The Athenian philosopher Epicurus observed families and proposed the contribution of both males and females of hereditary characters ("sperm atoms"), noticed dominant and recessive types of inheritance and described segregation and independent assortment of "sperm atoms".[3]

In the Charaka Samhita of 300CE, ancient Indian medical writers saw the characteristics of the child as determined by four factors: 1) those from the mother's reproductive material, (2) those from the father's sperm, (3) those from the diet of the pregnant mother and (4) those accompanying the soul which enters into the fetus. Each of these four factors had four parts creating sixteen factors of which the karma of the parents and the soul determined which attributes predominated and thereby gave the child its characteristics.[4]

In the 9th century CE, the Afro-Arab writer Al-Jahiz considered the effects of the environment on the likelihood of an animal to survive.[5] In 1000 CE, the Arab physician, Abu al-Qasim al-Zahrawi (known as Albucasis in the West) was the first physician to describe clearly the hereditary nature of haemophilia in his Al-Tasrif.[6] In 1140 CE, Judah HaLevi described dominant and recessive genetic traits in The Kuzari.[7]

The preformation theory is a developmental biological theory, which was represented in antiquity by the Greek philosopher Anaxagoras. It reappeared in modern times in the 17th century and then prevailed until the 19th century. Another common term at that time was the theory of evolution, although "evolution" (in the sense of development as a pure growth process) had a completely different meaning than today. The preformists assumed that the entire organism was preformed in the sperm (animalkulism) or in the egg (ovism or ovulism) and only had to unfold and grow. This was contrasted by the theory of epigenesis, according to which the structures and organs of an organism only develop in the course of individual development (Ontogeny). Epigenesis had been the dominant opinion since antiquity and into the 17th century, but was then replaced by preformist ideas. Since the 19th century epigenesis was again able to establish itself as a view valid to this day.[8][9]

In the 18th century, with increased knowledge of plant and animal diversity and the accompanying increased focus on taxonomy, new ideas about heredity began to appear. Linnaeus and others (among them Joseph Gottlieb Klreuter, Carl Friedrich von Grtner, and Charles Naudin) conducted extensive experiments with hybridisation, especially hybrids between species. Species hybridizers described a wide variety of inheritance phenomena, include hybrid sterility and the high variability of back-crosses.[10]

Plant breeders were also developing an array of stable varieties in many important plant species. In the early 19th century, Augustin Sageret established the concept of dominance, recognizing that when some plant varieties are crossed, certain characteristics (present in one parent) usually appear in the offspring; he also found that some ancestral characteristics found in neither parent may appear in offspring. However, plant breeders made little attempt to establish a theoretical foundation for their work or to share their knowledge with current work of physiology,[11] although Gartons Agricultural Plant Breeders in England explained their system.[12]

Between 1856 and 1865, Gregor Mendel conducted breeding experiments using the pea plant Pisum sativum and traced the inheritance patterns of certain traits. Through these experiments, Mendel saw that the genotypes and phenotypes of the progeny were predictable and that some traits were dominant over others.[13] These patterns of Mendelian inheritance demonstrated the usefulness of applying statistics to inheritance. They also contradicted 19th-century theories of blending inheritance, showing, rather, that genes remain discrete through multiple generations of hybridization.[14]

From his statistical analysis, Mendel defined a concept that he described as a character (which in his mind holds also for "determinant of that character"). In only one sentence of his historical paper, he used the term "factors" to designate the "material creating" the character: " So far as experience goes, we find it in every case confirmed that constant progeny can only be formed when the egg cells and the fertilizing pollen are off like the character so that both are provided with the material for creating quite similar individuals, as is the case with the normal fertilization of pure species. We must, therefore, regard it as certain that exactly similar factors must be at work also in the production of the constant forms in the hybrid plants."(Mendel, 1866).

Mendel's work was published in 1866 as "Versuche ber Pflanzen-Hybriden" (Experiments on Plant Hybridization) in the Verhandlungen des Naturforschenden Vereins zu Brnn (Proceedings of the Natural History Society of Brnn), following two lectures he gave on the work in early 1865.[15]

Mendel's work was published in a relatively obscure scientific journal, and it was not given any attention in the scientific community. Instead, discussions about modes of heredity were galvanized by Darwin's theory of evolution by natural selection, in which mechanisms of non-Lamarckian heredity seemed to be required. Darwin's own theory of heredity, pangenesis, did not meet with any large degree of acceptance.[16][17] A more mathematical version of pangenesis, one which dropped much of Darwin's Lamarckian holdovers, was developed as the "biometrical" school of heredity by Darwin's cousin, Francis Galton.[18]

In 1883 August Weismann conducted experiments involving breeding mice whose tails had been surgically removed. His results that surgically removing a mouse's tail had no effect on the tail of its offspring challenged the theories of pangenesis and Lamarckism, which held that changes to an organism during its lifetime could be inherited by its descendants. Weismann proposed the germ plasm theory of inheritance, which held that hereditary information was carried only in sperm and egg cells.[19]

Hugo de Vries wondered what the nature of germ plasm might be, and in particular he wondered whether or not germ plasm was mixed like paint or whether the information was carried in discrete packets that remained unbroken. In the 1890s he was conducting breeding experiments with a variety of plant species and in 1897 he published a paper on his results that stated that each inherited trait was governed by two discrete particles of information, one from each parent, and that these particles were passed along intact to the next generation. In 1900 he was preparing another paper on his further results when he was shown a copy of Mendel's 1866 paper by a friend who thought it might be relevant to de Vries's work. He went ahead and published his 1900 paper without mentioning Mendel's priority. Later that same year another botanist, Carl Correns, who had been conducting hybridization experiments with maize and peas, was searching the literature for related experiments prior to publishing his own results when he came across Mendel's paper, which had results similar to his own. Correns accused de Vries of appropriating terminology from Mendel's paper without crediting him or recognizing his priority. At the same time another botanist, Erich von Tschermak was experimenting with pea breeding and producing results like Mendel's. He too discovered Mendel's paper while searching the literature for relevant work. In a subsequent paper de Vries praised Mendel and acknowledged that he had only extended his earlier work.[19]

After the rediscovery of Mendel's work there was a feud between William Bateson and Pearson over the hereditary mechanism, solved by Ronald Fisher in his work "The Correlation Between Relatives on the Supposition of Mendelian Inheritance".

In 1910, Thomas Hunt Morgan showed that genes reside on specific chromosomes. He later showed that genes occupy specific locations on the chromosome. With this knowledge, Alfred Sturtevant, a member of Morgan's famous fly room, using Drosophila melanogaster, provided the first chromosomal map of any biological organism. In 1928, Frederick Griffith showed that genes could be transferred. In what is now known as Griffith's experiment, injections into a mouse of a deadly strain of bacteria that had been heat-killed transferred genetic information to a safe strain of the same bacteria, killing the mouse.

A series of subsequent discoveries led to the realization decades later that the genetic material is made of DNA (deoxyribonucleic acid) and not, as was widely believed until then, of proteins. In 1941, George Wells Beadle and Edward Lawrie Tatum showed that mutations in genes caused errors in specific steps of metabolic pathways. This showed that specific genes code for specific proteins, leading to the "one gene, one enzyme" hypothesis.[20] Oswald Avery, Colin Munro MacLeod, and Maclyn McCarty showed in 1944 that DNA holds the gene's information.[21] In 1952, Rosalind Franklin and Raymond Gosling produced a strikingly clear x-ray diffraction pattern indicating a helical form. Using these x-rays and information already known about the chemistry of DNA, James D. Watson and Francis Crick demonstrated the molecular structure of DNA in 1953.[22] Together, these discoveries established the central dogma of molecular biology, which states that proteins are translated from RNA which is transcribed by DNA. This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses.

In 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene: the gene for bacteriophage MS2 coat protein.[23] Richard J. Roberts and Phillip Sharp discovered in 1977 that genes can be split into segments. This led to the idea that one gene can make several proteins. The successful sequencing of many organisms' genomes has complicated the molecular definition of the gene. In particular, genes do not always sit side by side on DNA like discrete beads. Instead, regions of the DNA producing distinct proteins may overlap, so that the idea emerges that "genes are one long continuum".[24][25] It was first hypothesized in 1986 by Walter Gilbert that neither DNA nor protein would be required in such a primitive system as that of a very early stage of the earth if RNA could serve both as a catalyst and as genetic information storage processor.

The modern study of genetics at the level of DNA is known as molecular genetics and the synthesis of molecular genetics with traditional Darwinian evolution is known as the modern evolutionary synthesis.

See the article here:
History of genetics - Wikipedia

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Maze Therapeutics, a company translating genetic insights into new precision medicines, today revealed its first three lead therapeutic candidates in the companys wholly owned pipeline. The candidates include:

Each of the three lead candidates was enabled by Mazes COMPASS platform, which uncovered important new findings for the genetic target, discerning which specific signals may be critical for the treatment of patients, and which are likely non-actionable. The Maze pipeline will have the potential to serve as precision medicines for rare diseases and mechanistically defined subsets of common diseases based on certain genetic drivers.

In addition, Maze is concurrently leveraging COMPASS to advance additional discovery-stage research programs across three main therapeutic areas of focus: metabolic, cardio/renal and neurological diseases. These programs will constitute a broad, diverse pipeline for Maze and will be a combination of wholly owned and partnership-led collaborations.

Maze was built by co-founders, including Charles Homcy and other preeminent thinkers in the field of genetics, on a bold vision to leverage growing knowledge of genetic drivers of disease in order to create precision medicines for the treatment of both rare and more common diseases, said Jason Coloma, Ph.D., president and chief executive officer of Maze. Since our founding, we have been leveraging insights from leading geneticists, combined with the growing availability of paired human genetic and clinical data, the evolution of functional genomic technologies and advances in computational power, to build our COMPASS platform in order to bring unique insights into efficient, genetics-based drug development. We are excited by the significant progress we have made with our platform and pipeline, bringing us an important step closer to our goal of delivering the right drug to the right patient at the right time.

Mazes therapeutic candidates are designed to: 1) target genes whose activity affects the phenotype associated with another, often distant, gene, referred to as genetic modifiers; 2) mimic the activity of protective genetic variants; 3) correct the effects of toxic genetic variants; or 4) leverage new genetic insights to address otherwise challenging drug targets.

COMPASS is a proprietary, purpose-built platform that combines human genetic data, functional genomic tools and data science technology to map novel connections between known genes and their influence on susceptibility, timing of onset and rate of disease progression. In addition, Maze is exploring applications of COMPASS in diseases of haploinsufficiency by identifying genetic mechanisms that increase levels of a deficient protein and translating them into therapeutics.

New findings using COMPASS helped fill in fundamental data gaps, turning known but challenging targets into exciting, differentiated approaches to the genetic drivers of disease for our first three programs, said Sarah Noonberg, M.D., Ph.D., chief medical officer of Maze. While it has been shown that targets with human genetic evidence are more likely to yield efficacious treatments, very few groups have had the capabilities to then turn genetic insights into viable drug programs. We believe our COMPASS platform, integrated with our extensive drug discovery capabilities, will allow us to accelerate the pace of therapeutic development, as well as increase the likelihood of producing therapies that provide meaningful clinical benefit for patients. We are excited to advance these initial programs and look forward to continued progress toward the clinic as efficiently as possible.

About Mazes Wholly Owned Programs

GYS1 Program for Pompe DiseasePompe disease is a rare, inherited autosomal recessive disorder with an incidence of approximately 1 in 40,000 live births in the U.S., and is estimated to affect 5,000 to 10,000 patients worldwide. It is caused by mutations in the GAA gene, which codes for an enzyme responsible for breaking down lysosomal glycogen into glucose. As a result of this mutation, glycogen accumulates in various tissues, particularly skeletal and cardiac muscle tissues, causing progressive weakness and respiratory insufficiency.

Maze is developing a novel, oral approach to treating Pompe disease by inhibiting the protein muscle glycogen synthase, which is encoded by the gene GYS1. Targeting this protein leads to reduction in the synthesis of glycogen, which is expected to restore glycogen balance through a mechanism called substrate reduction. While GYS1 has been a therapeutic target of interest, its attractiveness as a therapeutic target has been limited due to its structural complexity and uncertainties related to the tolerability of a long-term reduction in muscle glycogen levels. Critical insights derived from COMPASS have enabled Maze to overcome these challenges. Maze has interrogated the structurally complex protein to develop an oral inhibitor of muscle glycogen synthase, a target not previously addressable by small molecule therapies. Maze is rapidly progressing its GYS1 program toward an Investigational New Drug application and expects to initiate clinical trials in the first half of 2022.

APOL1 Program for Chronic Kidney DiseaseCKD affects approximately 37 million people in the U.S., including more than 700,000 patients who suffer from end-stage renal disease (ESRD), many of whom require chronic dialysis. Individuals of African ancestry are at an approximately 3.5-fold greater risk of developing ESRD than individuals of European ancestry. Previous studies have shown that two coding variants of the apolipoprotein L1 (APOL1) encoded by the gene APOL1 cause toxic gain-of-function variants and are important genetic drivers of kidney disease that are responsible for much of the increased risk for CKD and ESRD in individuals of African ancestry. There are currently no approved therapies that address the underlying causes of APOL1-associated CKD, and efficacious treatment options for individuals with APOL1 risk variants and CKD represent a significant unmet medical need.

Maze employed COMPASS to functionalize human genetic variants to uncover the underlying biology of the target and has designed a small molecule that corrects the effects of toxic gain-of-function variants to potentially enable a therapeutic solution. Maze plans to name the development candidate in early 2022.

ATXN2 Program for Amyotrophic Lateral SclerosisALS is a progressive and fatal neurodegenerative disease with a prevalence of approximately 16,000 patients in the U.S. Current available treatments for ALS primarily focus on providing symptomatic relief and have limited impact on disease progression. A high variability in disease phenotype and life expectancy is observed and believed to be related to the presence of genetic modifiers.

One of Mazes founders, Aaron Gitler, identified a potent genetic modifier, ATXN2, whose inhibition has been shown to limit the toxicity of a certain protein, TDP-43, which is involved in pathologic aggregates seen in up to 97% of all ALS cases. Maze is translating these important insights by developing a novel microRNA gene therapy that targets ATXN2 and has used the proprietary application of its functional genomics tools to optimize its properties. Maze plans to name the development candidate in early 2022.

About Maze TherapeuticsMaze Therapeutics is focused on translating genetic insights into new precision medicines for rare diseases and mechanistically defined subsets of common diseases. Maze has developed the COMPASS platform, a proprietary, purpose-built platform that combines human genetic data, functional genomic tools and data science technology to map novel connections between known genes and their influence on susceptibility, timing of onset and rate of disease progression. Using COMPASS, Maze is building a broad portfolio, including wholly owned programs targeting Pompe disease, chronic kidney disease and amyotrophic lateral sclerosis, as well as partnered programs in cardiovascular and ophthalmic diseases. Maze is based in South San Francisco. For more information, please visit mazetx.com, or follow us on LinkedIn.

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Maze Therapeutics Reveals Its Initial Three Lead Programs Targeting Underlying Genetic Drivers of Life-Threatening Diseases - Business Wire

Background: An identical homozygous missense variant in EIF3F, identified through a large-scale genome-wide sequencing approach, was reported as causative in nine individuals with a neurodevelopmental disorder, characterized by variable intellectual disability, epilepsy, behavioral problems and sensorineural hearing-loss. To refine the phenotypic and molecular spectrum of EIF3F-related neurodevelopmental disorder, we examined independent patients.

Results: 21 patients were homozygous and one compound heterozygous for c.694T>G/p.(Phe232Val) in EIF3F. Haplotype analyses in 15 families suggested that c.694T>G/p.(Phe232Val) was a founder variant. All affected individuals had developmental delays including delayed speech development. About half of the affected individuals had behavioral problems, altered muscular tone, hearing loss, and short stature. Moreover, this study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum. Minor dysmorphic features were observed, although neither the individuals' facial nor general appearance were obviously distinctive. Symptoms in the compound heterozygous individual with an additional truncating variant were at the severe end of the spectrum in regard to motor milestones, speech delay, organic problems and pre- and postnatal growth of body and head, suggesting some genotype-phenotype correlation.

Conclusions: Our study refines the phenotypic and expands the molecular spectrum of EIF3F-related syndromic neurodevelopmental disorder.

Keywords: Altered muscular tone; Behavioral difficulties; Deafness; EIF3F gene; Neurodevelopmental disorder; Short stature.

Link:
EIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum - NCBI

SARATOGA SPRINGS, N.Y. Skidmores Pre-College program will be offered as a virtual experience this summer, allowing high school students and their families flexibility and ease of access as they get a head start on college.

Through the program, which runs July 5 through Aug. 6, students will immerse themselves in college-level academics, earn college credit and an official transcript, learn skills for navigating life as a future college student, and make connections with peers from around the world.

In addition to enrolling in one course for up to four credits, participants receive access to virtual Skidmore Admissions workshops on choosing a college, applying to college, writing an admissions essay and other tips and insights into college life. They can also attend virtual extracurricular events and campus tours and get full access to college resources such as academic advising and tutors in Skidmores Philip Boshoff Writing Center.

Skidmore Pre-College course offerings span the humanities, social and natural sciences, studio art and a diverse range of special topics that allow students to explore their interests or get ahead in a particular academic area.

The college-level curriculum can be challenging, but faculty mentorship and small class sizes provide additional opportunities for support and feedback that are unique to the Skidmore experience. Skidmore Pre-College students are one of 100 or fewer students, versus one of 1,000 or more at other institutions.

"There is nothing more delightful than to see how students form bonds by working together in these small and intensive summer courses, and to see these relationships continue to strengthen in college," said associate professor of history Jenny Day, who will teach History of Modern Japan during this year's five-week session, in a press release

Offering the program virtually also presents an exciting new opportunity for students and faculty, according to director Michelle Paquette-Deuel. I am eager for students this summer to learn from our outstanding faculty within the rigorous and collaborative online environment developed this past year, she said in the release.

In teaching his Human Genetics and Lab course, biology professor Bernie Possidente will assign some independent work, use the Zoom platform for class discussions and one-on-one meetings, and assign virtual labs and simple home experiments he has developed over the past three semesters since the start of the COVID-19 pandemic.

I try to model equal parts of doing science and being inspired by it, Possidente said in the release, and I like to give students as much flexibility and personal responsibility for their education as they can handle.

Senior physics instructor Jill Linz, who will be teaching Physics: Sound and Music with Lab this summer, finds it rewarding to see her students gain confidence and begin looking forward to their time as an undergraduate.

For high school students, there is an air of mystery surrounding college, she said in the release. They leave the Skidmore Pre-College program with a sense of accomplishment and maturity surrounding the entire college experience.

Fiona Promisel 24, now a full-time undergraduate at Skidmore College, agrees. She says the five-week program greatly enhanced her preparedness and transition to college life.

I found it to be an extremely valuable experience, she said in the release. I took classes with actual professors and Skidmore students, allowing me to get a true feel for how Skidmore operates.

Current high school sophomores, juniors and seniors can now apply to the Skidmore Pre-College program, and decisions will be made on a rolling basis. The scholarship application deadline is April 1, and all other applicants should apply by June 1.

Partial scholarships are awarded based on need and merit. To be considered, students must submit a completed program application and the scholarship application, available online at http://www.skidmore.edu/precollege/tuition.php#scholarshipaward.

Getting early access to college-level learning can be life-changing for so many students, Paquette-Deuel added. It affirms they can do the work. And it cannot be understated how transformative this is when you have a transcript in hand that you succeeded in a program like this, opportunities follow.

In the most recent rankings published by College Consensus, Skidmores Pre-College program was listed No. 7 among the top 30 pre-college programs in the nation.

More information about the program can be found online at the Skidmore Pre-College website at http://www.skidmore.edu/precollege.

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Skidmore Pre-College program to be offered as virtual experience in summer - The Saratogian

CODEXs spatial phenotyping capabilities will contribute to HCA investigators ability to build comprehensive tissue maps.

MARLBOROUGH, Mass.--(BUSINESS WIRE)-- Akoya Biosciences Inc., The Spatial Biology Company, today announced its support for the Human Cell Atlas (HCA) initiative, offering the CODEX solutions single-cell, whole-tissue imaging capabilities to HCA members under favorable commercial terms. Currently, there are more than 2,000 members of the HCA consortium.

The mission of the Human Cell Atlas is to create comprehensive reference maps of all human cells to describe and define the cellular basis of health and disease. Highly multiplexed, single-cell analysis methods allow biological researchers to catalogue the vast diversity of cellular phenotypes in a sample. In addition, HCA researchers also analyze the spatial and geographical context of individual cells across entire tissue sections.

Detailed spatial investigation of the cells in human tissues is allowing HCA researchers to study how cells function and interact at the molecular level, helping to create a 3D map of the body and gain insight into how cells such as immune cells communicate with healthy or diseased cells. Effective spatial methods are needed to enable this, said Dr. Sarah Teichmann, Ph.D., Co-Chair of the Organizing Committee for the International HCA and Head of Cellular Genetics at the Wellcome Sanger Institute.

Akoyas CODEX platform generates high resolution maps of millions of cells from each tissue section, enabling comprehensive spatial phenotyping.

Dr. Kai Kessenbrock, Assistant Professor at the Chao Family Comprehensive Cancer Center, University of California, Irvine, and an HCA investigator, added, As part of the Human Breast Cell Atlas Project, weve been complementing single-cell sequencing modalities with single-cell imaging data from the CODEX platform, so we can put the cellular diversity in context. This deep resolution allows us to investigate where in the tissue these cell types are located and how they organize into functional cellular neighborhoods, thus influencing tissue biology. Spatial phenotyping is a critical next step in single-cell biology which can be used to build a comprehensive cell atlas of human tissues.

Spatial phenotyping complements single-cell RNA-Seq-driven cell phenotyping, and when conducted on Akoyas CODEX platform, it enables researchers to get an expansive, multi-omics view of cell biology.

The value of the CODEX platform is to provide unbiased, whole tissue and single-cell imaging, which could greatly contribute towards building a cell atlas and advancing the mission of the Human Cell Atlas initiative, said Brian McKelligon, CEO of Akoya. As the newest commercial supporter of the HCA, Akoya will add this powerful capability to the HCA investigator networks spatial toolkit to assist them in developing a comprehensive cell atlas, with spatial context.

Dr. Kai Kessenbrock will share the latest Human Breast Cell Atlas data in an upcoming Nature webinar titled, Human Cell Atlas: A spatially resolved map of human breast tissue, on Tuesday, March 30 at Noon Eastern / 9 a.m. Pacific. To register for this event, please visit: akoyabio.com/HCAwebinar.

About Akoya Biosciences As The Spatial Biology Company, Akoya Biosciences mission is to bring context to the world of biology and human health through the power of spatial phenotyping. The company offers comprehensive single-cell imaging solutions that allow researchers to phenotype cells with spatial context and visualize how they organize and interact to influence disease progression and treatment response. Akoya offers two distinct solutions, the CODEX and Phenoptics platforms, to serve the diverse needs of researchers across discovery, translational and clinical research. To learn more about Akoya, visit http://www.akoyabio.com

View source version on businesswire.com: https://www.businesswire.com/news/home/20210323005375/en/

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Akoya to Help Support the Human Cell Atlas (HCA) Initiative with Single-Cell, Spatial Imaging Capabilities - BioSpace

The Baltimore BioCrew is a team of high school students who are tackling real-life problems in genetics and biology through research, lab work and creativity. Every year, the team competes in the high school division of the International Genetically Engineered Machine (iGEM) competition.

The projects emphasize synthetic biology concepts, with previous examples including arsenic biosensors for drinking water, pigmented bacteria and a detector kit for flavobacteria in fish farms. Last year there were nearly 250 competing teams from around the world, high school to graduate level. The BioCrew gold medaled for its work in last year and received a special nomination for Best Integrated Human Practices.

This year, the BioCrews project focused on phytoplankton. Phytoplankton play a significant role in absorbing atmospheric carbon and producing oxygen. Unfortunately, they cannot grow in areas of the ocean with low iron concentrations. The BioCrew aimed to engineer cyanobacteria (blue-green algae) to transport iron into cells to help phytoplankton grow. Unfortunately, its wet lab work was hindered by the pandemic.

In a typical week during the school year, students spend three hours in the lab on Saturdays. During the summer, these hours increase to seven. These lab hours usually allow students to learn techniques, brainstorm, bond and do the experiments they need to complete their project.

Due to COVID-19 safety guidelines, the BioCrew members found ways to make the science portable so they could still get the data they needed. For example, some students took cyanobacteria samples to grow at home; this was safe because cyanobacteria is a biosafety level 1 organism. The students then tracked the growth of the cyanobacteria at different iron concentrations by measuring the cell density with homemade Secchi sticks.

There were also some aspects of the project that could be easily conducted over Zoom. For example, the integrated human practices team reached out to various experts and community members throughout the project to ask for feedback and advice. These interviews were conducted virtually. The BioCrew conducted classes for middle schoolers along with a social media education campaign to teach the public about the project.

Wangui Mbuguiro has mentored the Baltimore BioCrew team for three years. She is a Biomedical Engineering PhD student at Hopkins. In an email to The News-Letter, she explained how the changes brought on by the pandemic shed light on new ways for the BioCrew to move forward and do science.

Synthetic Biology and iGEM is about making science and technology accessible in different spaces. Designing safe and feasible experiments that can be done at home to gain new insight is really pushing toward that accessibility, she wrote. I think optimizing at-home experiments will be an even larger portion of our project this year, regardless of our increased access to lab.

The old-school homemade technology like the Secchi sticks was also a nice reminder that science wasnt always done with the technology we have today, according to Mbuguiro. Theres a long legacy of other technologies and methods that the team can lean on when having to adapt to at-home experiments and not having access to the labs resources.

Shantika Bhat is a senior at Baltimore Polytechnic Institute, and this is her second year on the team. In an interview with The News-Letter, she said her favorite thing about being part of the BioCrew team is getting the opportunity to work with different students in Virginia and Maryland.

Bhat works in integrated human practices, which means she often contacts and communicates with experts and community members for the team.

According to Bhat, while the pandemic did limit the projects and experiments that the team members could do, it also led them to learn other skills like website development and social media to educate the public.

The main takeaway Bhat gained from her time on the integrated human practices team is the confidence to reach out and learn from experts.

Im going to continue to put myself out there because if I didnt, I wouldnt have been able to connect to and talk to all these people, she said. If I wasnt bold, I wouldnt have gotten those opportunities.

For Mbuguiro, her favorite part of the experience has been collaborating with her peers and mentees.

Working with the students in the BioCrew and the other mentors always manages to re-spark my excitement, curiosity and creativity in doing science, she wrote.

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How high school scientists in Baltimore have adapted to the pandemic - Johns Hopkins News-Letter

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This was the moment of truth. Wed spent countless hours meticulously sterilising seeds (1,710, to be specific), filling the lab with a cacophony of rattling as we shook them in bleach. Wed built a fungus city: great tower-blocks of petri dishes stacked on the lab workbenches, with different colours, textures and shapes of fungi all emerging inside. Wed extracted enough DNA that the freezer, stuffed full of tubes, threatened to revolt.

Finally the time had come for me to analyse all the data, and discover just what wed managed to find after all these months of work. In the first study of its kind, to our knowledge, in a major seed bank, we found hundreds of fungi hidden inside seeds from the Millennium Seed Bank, some of which are likely to be species new to science and could be crucial for the future of plant health.

I cant remember the moment when I first decided to study fungi. If only I had an anecdote about my time as a biology undergraduate looking down the microscope at some spores for the first time, overcome by their sheer majesty but that would be fiction. For one thing, fungi barely appeared in my degree, and when they did it was usually in the negative context of causing disease.

Given that fungi are a whole kingdom of species which, alongside animals and plants, belong to the major domain of planet Earths multicellular life together called the eukaryotes, this is perhaps surprising. Yet this is the typical experience in both school and higher education (in the UK and the US at least) and, unsurprisingly, when you dont teach students about fungi, they dont go on to study fungi. Which leads to fewer researchers studying fungi that can teach students about fungi and you get the picture.

I really cant emphasise enough how much of an oversight this is. The latest estimate of the total number of fungal species is 6.2 million. To put that in context, that would mean our planet is inhabited by 15 times more fungi than plants. Other recent estimates for fungal diversity have ranged widely from 2.2 million to 165 million species but no matter which you go with, the numbers are all far greater than the 150,000 fungi which scientists have already found and described.

Weve barely scratched the surface, and I mean that quite literally countless fungi will be underground and inside other organisms. These microscopic fungi, or more simply microfungi, are invisible to the naked eye, and so for a long time have remained under the radar. But that doesnt mean theyre unimportant. Quite the opposite.

Yes, some will be pathogens, which can cause disease in plants and animals. These tend to be the fungi that get the most attention, both in terms of public awareness and scientific research, and not without some good reason. With our increased global travel and trade, not to mention our contributions to climate change, were creating a perfect opportunity for new fungal pathogens to emerge and thrive.

But theres so much more than just the pathogens. There are also the recyclers (saprotrophs), which break down organic matter and return nutrients to the soil in the continuous cycle of life and death. We live on a planet of finite resources, so its thanks to these little fungi doing the work to recycle them that our natural world can exist at all.

Countless fungi play key roles in modern society: they can be a source of medicines such as antibiotics and immunosuppressants, industrial enzymes for detergents and manufacturing and new biomaterials to replace plastics. Even the humble bakers yeast, which underpins our everyday food and drink, can be used in the lab to study human genetics or modified to produce important compounds. And these are just the fungi we already know about imagine the useful properties awaiting discovery in the fungi we are yet to find.

And maybe most famously there are the symbiotic partners known as mycorrhizal fungi, which form a relationship with plant roots, usually for mutual benefit: they can help the plant take up water and nutrients in return for carbohydrates. These fungi can form vast underground networks of nutrient exchange between plants, popularly known as the wood wide web. As if that wasnt enough, mycorrhizal fungi also help to increase the amount of carbon stored in the soil, and so play an important role in regulating global climate.

Which brings me to the fungi I study. Mycorrhizal fungi arent the only ones to be found when we look at plants. All plant tissues contain fungi, in much the same way that us animals have an array of microorganisms living inside us: our microbiome. These microfungi of plants are called fungal endophytes (endo=in, phyte=plant), and are defined by the fact that they live inside plants without causing any visible symptoms of disease.

The sequencing revolution, which has enabled us to detect otherwise imperceptible organisms from mere traces of their DNA, has transformed our awareness of these microscopic fungi. A single plant individual is capable of hosting countless different fungal species.

As always, however, its not all that simple. When we find fungal endophytes inside healthy plants, some may be latent decomposers or pathogens in other words, they are in a dormant state, waiting for the plant to die so that they can decay it, or for an opportunity to cause disease. At the same time, there are other fungal endophytes which we know can actually help their plant host, for instance by improving germination and seedling growth. What we call the endophyte lifestyle is really more of a spectrum of interactions between plants and fungi, with both good and bad consequences for plant health.

It was these fungi, with all their mystery and potential, that captured my interest. Against the odds I did find my way to studying fungi, which started in earnest when I was lucky enough to get an undergraduate sandwich year placement at Londons Royal Botanic Gardens Kew with a senior scientist of fungal research, Ester Gaya. Im still based there today, almost seven years later.

And then there is the Millennium Seed Bank, which is also part of Kew. If anything, the term seed bank probably conjures up an image of the Svalbard Global Seed Vault: a vast concrete monolith emerging out of the Arctic snow like some sort of super-villain base.

The Millennium Seed Bank, nestled in the grounds of Wakehurst Place in the UK countryside, is rather less imposing to look at, but perhaps even more impressive inside. Coordinated by Kew, the seed bank is both a physical building the largest seed bank in the world with over 2.3 billion seeds from almost 40,000 species as well as a global partnership dedicated to the collection and conservation of seeds worldwide.

Seed banks are just what they sound like a place to store seeds long-term as insurance against potential crises. And crisis is on the horizon: thanks to climate change and our unsustainable use of the planet, two in five plants are estimated to be threatened with extinction. The mission of the Millennium Seed Bank is to find and preserve seeds of wild plants before theyre lost for good.

Seed banking is not just a backup for a hypothetical future scenario, as collections can already be put to good use collecting seeds from different native communities, for instance, will be crucial for ecosystem recovery after wildfires and for successful reforestation.

A fungal perspective puts a whole new spin on the idea of seed banking. It may not have been the primary goal, but in the process of preserving plant diversity, seed banks are also preserving the fungal diversity inside seeds. Of course, scientists working in seed banking have been aware of fungi before now, but the context has been decidedly negative. The banking standards from the Food and Agriculture Organization of the United Nations always refer to fungi as a contamination, a problem to be removed, and actually recommend use of fungicides to kill any fungi present.

This approach is rooted in reason, as many fungi can and will cause disease in plants, and a seed bank needs to avoid becoming a vector for plant diseases. But were increasingly realising that the microorganisms in and around us influence the world far more than previously understood. As humans, altering the balance of microorganisms in our gut can have all sorts of negative health consequences and has even been connected to neurological disease. We know less about the microbiome of plants, but this will need to change if we are to successfully protect all the species at risk of extinction.

The idea that the Millennium Seed Bank must surely be full of these potentially helpful microfungi we call endophytes inside its seeds would not be a stretch to anybody who studies fungi or microbiology, and yet no one had ever looked before. This changed a few years ago, when Gaya first started to consider the question. But where to start, in such an enormous collection of seeds?

Our opportunity came thanks to a fellow PhD student, Simon Kallow, who studies how to store the seeds of banana wild relatives long-term for conservation. As the name suggests, crop wild relatives are the close relatives of our cultivated crops. Theyre interesting to scientists as theyre far more genetically diverse and so can provide a source of useful traits to breed into our crops, for instance to make them more resilient to climate change, pests or disease.

Theres another idea that the microbiome of wild relatives could also have a role to play in protecting our crops: that we can potentially introduce endophytes from wild relatives into crops to pass on useful properties, such as stress tolerance. Protecting wild relatives, and their microbiomes, can be seen as a safeguard for the future of the crops we all rely on for food.

This is particularly relevant for bananas, which are not only an important cash crop worth US$31 billion a year but also a significant part of peoples diets in the regions where they grow. In an unfortunate case of history repeating itself, global banana crops are currently threatened by a fungal pathogen strain called Foc TR4, and so its doubly important to conserve their wild relatives.

Kallow was interested in what fungal endophytes might be inside his wild banana seeds, and if they could be playing a role in how well the seeds survived storage and went on to germinate. It was the perfect chance for us to have a first look at what fungi might be hidden inside the Millennium Seed Bank collections.

We used two approaches we crushed up seeds and sequenced any fungal DNA from inside, but we also tried to grow the fungi from inside seeds, known as culturing. That way, we captured as much of the diversity that was present as possible but also built a collection of living fungal endophyte cultures that we can use in the future.

The reality of working with organisms that are too small to see can be a little anticlimactic a lot of the time youre just looking at tiny amounts of colourless liquid in tubes.

In looking at just six plant species, we were able to find almost 200 fungal species. Extrapolate up to the Millennium Seed Banks 40,000 plant species and even if assuming there is some overlap of fungal endophytes between different plant species you can end up with a heady estimate of fungal diversity hidden in their collections, potentially reaching over a million species, some of which are likely new species to science.

Mining that diversity is intrinsically interesting in terms of studying the fungi themselves, but these are also species that may be important to the health of the plants they inhabit, and therefore crucial to the objectives of seed banking at large.

As we were able to grow some fungal endophytes in culture, we know that at least some species (mostly the very common ones) can survive the Millennium Seed Banks protocol of processing, drying and freezing seeds. There were other endophytes that we detected from sequencing their DNA, but which didnt grow in culture but these werent necessarily dead, as many fungi are more sensitive and dont grow readily in the lab. In the future we will need to figure out the true extent of endophytes surviving the storage process in case there are important, rare species that are lost.

Our results support previous studies which suggest that fungi are usually mutually exclusive inside seeds. In other words, in most cases where we detected fungi inside the seeds, we only found a single species, suggesting that in the limited space of the seed one fungal species can often dominate and outcompete any others.

This raises an interesting question as to whether we can use this phenomenon to protect our plants from pathogens: if we can inoculate a plant with the right fungal endophyte, could it outcompete fungal pathogens that try to infect the seed? This idea needs to be tested in experiments, but its one example of why there is hope that we can use endophytes for a natural form of plant disease control.

We also found that the total number of fungal endophytes present in each set of seeds, as well as the specific combination of species, changed depending on the habitat that the seeds were collected from. This means that when researchers are working in the field, where they choose to collect seeds from can have unforeseen consequences on what microbiome will be preserved.

The proportion of seeds which were alive or germinated after storage also changed depending on habitat. Hopefully future experiments can confirm if the fungi themselves are contributing to this pattern. This is why its so valuable to have preserved living fungal cultures, as it allows us to use them in experiments to test many of these questions.

As is so often the case in science, we emerged from this study with more questions than answers. But some of these questions, which have consequences for the way we protect seeds for the future, have never been researched before at the Millennium Seed Bank. Are we managing to preserve enough of the seed microbiome? How much will that matter for the plants health?

And then there are the questions about the fungi themselves what can we learn from this previously unexplored gold mine of fungal diversity?

To rise to the challenge, in the first instance, we need to ensure people have the opportunity to learn about them a different experience from what I had, barely hearing about fungi in university, and not at all at school.

In the summer of 2019 I helped to run the fungi stall at Kews Science Festival, an annual public event where visitors are invited to take part in activities and talk to scientists about why plants and fungi are so important to our lives. I will always remember the wide-eyed looks as I explained that the biggest organism in the world is actually a 400-tonne, 2,500 year old humongous fungus, or that some mushrooms glow in the dark to attract insects.

Fungi are strange and cool and interesting enough that really all you have to do is share them and fascination will follow. Children and adults alike would approach our stall knowing almost nothing about fungi, but by the end of the weekend, fungi were among the top mentions of what visitors enjoyed most at the festival.

You can find amazing things once your eyes are opened to this weird and wonderful kingdom.

This article was originally publishedin the Conversation on 22 March 2021.

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SE - How we discovered a hidden world of fungi inside the world's biggest seed bank - QMUL