Centre for Molecular Biosciences & Genomics’ Post

The science here is so cool that I have to make a note of this advance in biomedical technology and treatment. The Food and Drug Administration approved a gene editing treatment for sickle cell anemia last week. Sickle cell anemia is a genetic disease caused by a single recessive allele. Having two copies of the gene is highly deleterious – that genotype causes sickle cell anemia, in which malformed red blood cells interfere with circulation and cause debilitating pain, organ failure, and cardiovascular disease. There’s an interesting evolutionary biology story here, too. Because the gene is so harmful, we might expect it to be eliminated from our population over time. But a single copy of the gene confers resistance to malaria. The plasmodium parasite that causes malaria has a hard time affecting red blood cells that carry just one copy of the gene. In places where malaria is endemic, heterozygotes have a fitness advantage. The genes for sickle cell therefore remain relatively common in populations. This is true for much of Africa, including the regions from which people were captured and forced into slavery in the United States. That history of evolutionary biology and slavery has combined to make sickle cell disease much more common for Black Americans than for other Americans. The CRISPR/Cas9 system uses a combination of bacterial and viral mechanisms to precisely edit the genes of all cells in a living organism’s body. Cas9 is a naturally occurring enzyme in bacteria. It’s a nuclease – an enzyme that cuts up DNA. When some bacteria are infected by a virus, they can produce matching RNA sequences to the viral DNA, which Cas9 can then target, chop up, and deactivate. Recently, scientists realized that we could use Cas9 to precisely cut up DNA in people, using a customized RNA sequence to target the spot in the genome that we want to make a cut. We can cut around a mutated gene that isn’t functioning properly and then insert a functional copy of the gene, which will fit into the cut ends of the DNA and result in an intact, functional genome to allow a patient to live a healthy life, free from that genetic disease. Of course, there are some downsides and caveats: 1. It’s incredibly expensive - but then, so is living with sickle cell disease 2. This treatment is difficult. Companies expect that they might be able to treat up to 10 patients per year given their current capabilities. 3. Long-term safety is also a concern, although we have data so far that indicates it's safe, and we'll continue collecting data. You can read more on my blog, with links for further information: https://lnkd.in/gpRQhs2V #cas9 #crispr #anemia #disease #hematology

Researchers at EMBL's European Bioinformatics Institute have made a breakthrough in understanding the genetic diversity of the deadly malaria parasite Plasmodium falciparum. They discovered a mechanism called "copy-paste" genetics that accelerates the parasite's genetic diversity, which explains why certain areas show high diversity while the rest of the genetic landscape remains ordinary. The study focused on two genes, DBLMSP and DBLMSP2, which encode surface proteins critical for immune evasion, which revealed an unusual genetic process called non-allelic gene conversion, where part of a gene sequence can be copied between different genes on the same DNA molecule. This process contributes to increased genetic diversity within the surface proteins of the parasite. To uncover the hidden genetic variants, the researchers developed new bioinformatics software that utilized genome graphs. This approach allowed them to identify multiple gene conversion events and discover previously unknown variants. These findings provide a valuable resource for the global malaria research community and shed light on how pathogens like P. falciparum evolve and evade the immune system.

A new study published in Nature by the Weizmann Institute of Science has revealed a bacterial immune system that alters the tails of phages, viruses that attack bacteria. - by Frederic Eger/Weizman Institute of Science - Phages have a head and a tail, with the head containing the phage's genetic material and the tail used to identify a potential host, a bacterial cell into which it can inject this material. Once the injection is complete, the phage hijacks the bacterium's cellular machinery and forces it to produce new copies of itself, which ultimately burst the cell and infect other bacteria in the colony. The first antiphage defense mechanisms in bacteria were discovered in the 1960s, but only a handful of such mechanisms were known until recently. The most famous of these is CRISPR-Cas9, whose discovery led to a revolution in gene editing. In recent years, there has been a wave of new findings in the field, leading to the discovery of more than 150 new bacterial immune systems with varied modes of action. Many of these systems were identified using a method developed by Prof. Rotem Sorek of Weizmann’s Molecular Genetics Department. Sorek’s method is based on a strikingly simple principle: Genes involved in bacterial immune mechanisms tend to cluster together in the bacterial genome, in areas known as “defense islands.” Researchers can discover new immune systems by examining genes with unknown function that are located close to known defense islands. This suggests that the evolutionary source of a large part of our innate immune system comes from bacteria. In the new study, researchers led by Dr. Jens Hör from Sorek’s laboratory discovered a new bacterial immune system that contains a ubiquitin-like protein with a structure similar to that of ISG15, one of the more mysterious proteins in the human immune system. ISG15 plays a role in the defense against different viruses, such as influenza and HIV, but how it performs its task is not entirely clear. To understand how the duplicated viruses lose their ability to infect other cells and what role the new bacterial immune system plays in this, Sorek’s research team joined forces with Dr. Sharon Wolf, head of the Electron Microscopy Unit in Weizmann’s Chemical Research Support Department. The researchers believe that this new immune system is capable of recognizing the three-dimensional structure of the viral tail, which allows the system to work effectively against a wide variety of phages, as long as they have tails with a similar structure. *** Gizel Maimon Head of Media Information & PR Section Department of Communications gizel.maimon@weizmann.ac.il

My journey into the world of genotypes began in secondary school, where I was introduced to the three types of genotypes, with mine being AS. This early fascination with biology propelled me into deeper exploration, eventually leading me to study human physiology. My passion for understanding genotypes evolved into a commitment to advocating for individuals affected by sickle cell anemia, inspired by the late Nura Abdullahi. Over the years, I've actively engaged in various advocacy initiatives on both local and international levels. I've organised "Know Your Genotype" (KYG) campaigns, led "Catch Them Young" initiatives, orchestrated blood donation drives, and coordinated World Sickle Cell Day events. Notably, for the past five years, I've spearheaded annual fundraisers every February 13th to procure essential medications for individuals living with sickle cell anemia in Zaria, Abuja, and Kaduna. This has led me to become a secondee in Lisbon on the Arise Initiative project, this opportunity I am thankful to Baba Inusa and the management of Sickle Cell Cohort Research for this opportunity. Funded by the EU under the H2020-MSCA-RISE-2018 programme African Research and Innovative Initiative for Sickle Cell Education(ARISE) focuses on enhancing research capacity and service improvement in sickle cell disease (SCD). In my role within ARISE, I contribute significantly to Work Package 7 (WP7) - Dissemination and Communication, where I drive awareness of the project's objectives and achievements across diverse audiences, from academia and clinical sectors to patients and national organizations. Additionally, my background in science (Human Physiology, Biotechnology and currently Epidemiology) has given me the privilege of learning at the Prof. Miguel's esteemed lab within Work Package 3 (WP3) of ARISE. This work package concentrates on enhancing laboratory diagnostics and quality assurance systems for population screening. I actively participate in learning educational programmes for population screening management, advancing techniques for haematological analysis, and proposing prevention programmes to enhance early management. My involvement in these initiatives reflects my unwavering commitment to improving the overall outcomes and quality of life for individuals affected by sickle cell anemia. I am excited about the transformative impact our collective efforts will have on healthcare outcomes, fostering international collaboration and advancing scientific research in this critical area. If you’re interested in the epidemiology, latest treatment regimen, service improvement and regular updates from industry experts on sickle cell anaemia visit ariseinitiative.org or follow ARISE social media pages for up to date information. Together we can end the sickle cell disease cycle. #research #AriseEuproject #sicklecelldisease

The Problem: we lack the knowledge, talent, and leadership to stop epidemics. The Solution: Train the next generation of virus hunters to learn the new and powerful molecular tools using the Scientific Method.  The Plan:  -The first step is to create the Golden Age of Virology https://lnkd.in/eVx2BjRx. Done. -The second step is to create the William H. Murphy Professorship, named for the University of Michigan scholar who discovered the key to unlocking the mysteries of viral epidemics. Prof. Murphy showed that genes that we inherited through evolution, ancestral genes, interact with foreign viruses to CAUSE a disease. This professorship spotlights the need for a new generation of virologists to be trained on how to unlock the mysteries behind the interactive relationship between viruses and their host’s genome. Done. Working with my colleagues at NIAMRRE, we plan to extend these observations to other critical areas, such as ancestral genes' role in antimicrobial resistance. We need both Scholars and Entrepreneurs. I would favor making academic courses available for future leaders on how to get your idea to the marketplace by understanding the complexities of the medical industry. If the startup bug bites, there are ways to get you in front of investors, but you must pass some entrepreneur accelerator courses. Shout out to the faculty of the John Pappajohn Entrepreneurial Center at The University of Iowa; they taught me how to pitch. My last pitch was with 34 other U-M alumni founders and it was truly humbling. Plug and Play University Pitch Sessions Thank you, Michigan Medicine, for making a half-century-old dream come true. If any breakthroughs are going to happen, they certainly will happen at the Department of Microbiology and Immunology, Ann Arbor, MI, the first Microbiology Department in the Americas, 1904. This department, a testament to our rich history and commitment to scientific excellence, is where the future of virology is being shaped. Michigan: The Leaders and Best. #venturecapital #angelinvestor #cancer #hivaids  #bioOS #biotechnology #diagnostics #innovation #technology #management #startups #liquidbiopsy #neurodegenerativediseases #multiplesclerosis #parkinsonsdisease #alzheimersdisease #longhaulers #longcovid #humangenome #onetestonelife #longevity #artificialintelligence #rna #rnaseq #personalizedprevention https://lnkd.in/efmxHgwQ

𝐔𝐍𝐕𝐄𝐈𝐋𝐈𝐍𝐆 𝐓𝐇𝐄 𝐆𝐄𝐍𝐄𝐓𝐈𝐂 𝐅𝐎𝐔𝐍𝐃𝐀𝐓𝐈𝐎𝐍𝐒 𝐎𝐅 𝐋𝐔𝐍𝐆 𝐀𝐃𝐄𝐍𝐎𝐂𝐀𝐑𝐂𝐈𝐍𝐎𝐌𝐀: 𝐀 𝐂𝐎𝐌𝐏𝐑𝐄𝐇𝐄𝐍𝐒𝐈𝐕𝐄 𝐆𝐄𝐍𝐎𝐌𝐄-𝐖𝐈𝐃𝐄 𝐀𝐒𝐒𝐎𝐂𝐈𝐀𝐓𝐈𝐎𝐍 𝐒𝐓𝐔𝐃𝐘 𝐀𝐂𝐑𝐎𝐒𝐒 𝐄𝐀𝐒𝐓 𝐀𝐒𝐈𝐀𝐍 𝐀𝐍𝐃 𝐄𝐔𝐑𝐎𝐏𝐄𝐀𝐍 𝐏𝐎𝐏𝐔𝐋𝐀𝐓𝐈𝐎𝐍𝐒 A recent landmark study titled "Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population" spearheaded by Jianxin Shi et al., signifies a monumental stride in cancer genetics. This research intricately maps the genetic predispositions contributing to lung adenocarcinoma (LUAD) within East Asian populations, while offering a comparative lens against European cohorts. Lung adenocarcinoma, as the most prevalent form of lung cancer globally, presents a complex etiological puzzle, with known risk variants explaining only a minuscule fraction of its heritability. Through a meticulous two-stage genome-wide association study (GWAS), the research unravels 12 novel susceptibility variants, expanding the total to 28 at 25 independent loci, and shines a light on the distinct genetic underpinnings of LUAD across different ancestries. 𝑴𝒆𝒕𝒉𝒐𝒅𝒐𝒍𝒐𝒈𝒊𝒄𝒂𝒍 𝑬𝒙𝒄𝒆𝒍𝒍𝒆𝒏𝒄𝒆 𝒂𝒏𝒅 𝑭𝒊𝒏𝒅𝒊𝒏𝒈𝒔 Employing a robust analytical framework, the study executed a two-phase GWAS meta-analysis across East Asian populations, encompassing 21,658 cases and 150,676 controls. This comprehensive approach not only identified novel genetic markers but also engaged in transcriptome-wide association analyses and colocalization studies to pinpoint candidate genes like FADS1 and ELF5. A critical aspect of this research lies in its comparative analysis with European populations, revealing a nuanced genetic landscape of LUAD susceptibility that diverges significantly across ancestries. 𝑵𝒐𝒗𝒆𝒍 𝑮𝒆𝒏𝒆𝒕𝒊𝒄 𝑰𝒏𝒔𝒊𝒈𝒉𝒕𝒔 𝒊𝒏𝒕𝒐 𝑳𝒖𝒏𝒈 𝑨𝒅𝒆𝒏𝒐𝒄𝒂𝒓𝒄𝒊𝒏𝒐𝒎𝒂 Among the groundbreaking discoveries, the study highlights 12 previously unidentified susceptibility variants that bolster our understanding of LUAD's genetic architecture in East Asians. Notably, the research delineates how these genetic variants manifest differently across ancestries, with a significant number showing no association in European populations. This disparity underscores the importance of tailored genetic studies reflective of specific ethnic backgrounds. 𝑻𝒉𝒆 𝑷𝒂𝒕𝒉 𝑭𝒐𝒓𝒘𝒂𝒓𝒅: 𝑻𝒓𝒂𝒏𝒔𝒍𝒂𝒕𝒊𝒐𝒏𝒂𝒍 𝑰𝒎𝒑𝒍𝒊𝒄𝒂𝒕𝒊𝒐𝒏𝒔 𝒂𝒏𝒅 𝑩𝒆𝒚𝒐𝒏𝒅 By elucidating the genetic intricacies of lung adenocarcinoma in East Asians, the study lays the groundwork for developing ancestry-specific risk assessment tools and therapeutic strategies. 𝑭𝒐𝒐𝒅 𝒇𝒐𝒓 𝑻𝒉𝒐𝒖𝒈𝒉𝒕: What role do genetic variations unique to East Asian populations play in lung adenocarcinoma's risk and progression compared to European populations, and how could this knowledge shape targeted global prevention and treatment strategies?

In genomics, sequencing techniques have revolutionized our understanding of biology, medicine, and genetics, including our ability to combat infectious diseases. From deciphering viral genomes to tracking pathogens, these tools are invaluable in fighting global health threats. 🔬 First-Generation Sequencing The Sanger method, developed by Frederick Sanger in 1977, laid the foundation for achievements like the Human Genome Project. This method, which involves chain-terminating nucleotides to generate DNA fragments, remains a gold standard for smaller-scale applications and validating other sequencing results. 💡 Next-Generation Sequencing (NGS) NGS platforms, such as Illumina's sequencers, revolutionized genomics. NGS technologies use high-throughput, parallel processing capabilities to rapidly and cost-effectively sequence entire genomes. This scalability and speed have enabled real-time surveillance and characterization of emerging pathogens. 🚀 Third-Generation Sequencing Techniques like Pacific Biosciences' SMRT sequencing and Oxford Nanopore Technologies' Nanopore sequencing represent the forefront of genomic research. These methods provide long read lengths, surpassing previous limitations and enabling comprehensive analysis of complex genomic regions and structural variations. Oxford Nanopore Sequencing (ONS) has been a game-changer, offering portable, real-time sequencing. During the COVID-19 pandemic, ONS allowed rapid sequencing of SARS-CoV-2 genomes at the point of care, facilitating immediate public health responses and tracking new variants. Similarly, during the 2014 Ebola outbreak, ONS enabled on-site sequencing of Ebola virus genomes, speeding up the response and aiding diagnostics and treatment development. Sequencing technologies have transformed public health, especially in infectious diseases. They enable precise pathogen identification, outbreak source tracking, and transmission dynamics monitoring. Sequencing supports developing targeted diagnostics, vaccines, and treatments by providing detailed genomic data. During the COVID-19 pandemic, sequencing data was critical in identifying mutations leading to new variants, shaping vaccination strategies and public health responses. Genomic surveillance of influenza viruses informs annual flu vaccine formulations, enhancing their effectiveness. As we push the boundaries of sequencing technology, our fight against infectious diseases grows stronger. Advances in sequencing pave the way for real-time, point-of-care diagnostics, personalized medicine, and comprehensive pathogen surveillance systems. Integrating sequencing data with artificial intelligence and machine learning holds potential for predictive analytics, early outbreak detection, and developing next-generation antimicrobial therapies. #Genomics #Sequencing #Biotechnology #NextGenSequencing #InfectiousDiseases #PublicHealth #Pandemics #COVID19 #Ebola #HealthcareInnovation #ScienceAndTechnology

To kick off our week we're delighted to have another mini-interview, this time with Esteban Alberto Gómez Cifuentes from William Harvey Research Institute. Esteban's work has recently featured in a fascinating paper about a genetic variation that could lead to increased risk of viral infections - the link to more information about that research is at the end of this interview. Who are you, and what are you working on? Hello! My name is Esteban Gomez, and I just did the viva of my PhD. I’m part of the Lipid Mediator Unit at the William Harvey Research Institute. My work is focused on the use of bioinformatics tools to understand better the mechanisms behind the resolution of inflammation. After inflammation, the body goes through different processes to reach homeostasis, the natural state of the body. A series of molecules, known as specialized pro-resolving mediators, are involved in the resolution steps by downregulated inflammatory molecules, helping immune cells to clear bacteria after infection, tissue repair, etc. My main interest are these mediators and how their dysregulation can lead to the development of human diseases. What part of your research makes you most excited? I love bioinformatics and being able to apply computational tools to resolve biological problems. In that sense, as part of my project, I was able to use machine learning, basically artificial intelligence, to identify pro-resolving mediators with the potential to predict the response to treatment for rheumatoid arthritis (RA). RA is a terrible disease that affects a great number of people worldwide, so thinking that my research can be the basis for developing diagnostic tools that can help the recovery of these patients excited me a lot. On the other hand, I always have been interested in genetic mutations and how they affect us. For example, what happens if there is a mutation that deletes a gene that is important for the resolution activity of the pro-resolving mediators? I have been working on identifying these genetic variants and exploring their biological consequences with very fascinating results. What’s coming up for you next? I have recently had a paper published in the journal ‘Blood’, which I’m very happy about. The paper is focused on a genetic variant that reduces the expression of LGR6, a receptor that is important for the activity of MaR1, one of the pro-resolving mediators. I was able to show that the loss of the receptor leads to the dysregulation of different resolution mechanisms and its link with a higher incidence of viral infection at the population level. It’s great to see my work published, especially with a discovery that can have a big impact on the resolution field. I invite everyone to read it! You can find out more about Esteban's research here: https://lnkd.in/ed3BC4MG #research #bioinformatics

📃Scientific paper: Forschung mit Krebsregistern – was geht, was (noch) nicht? Abstract: Background One of the tasks of state cancer registries is to provide data for research or one’s own research. Data is not collected in the cancer registry primarily for research, but with mandatory reporting and without the consent of the persons concerned for the fulfilment of legal tasks. Can data from cancer registries be meaningfully used for research, are they used and which framework conditions for data use should be improved? Methods Using PubMed®, the use of cancer registry data in scientific publications was determined for Germany and for the US Surveillance, Epidemiology, and End Results (SEER) program. Possibilities for data use were identified from state and federal laws. Results For Germany, 2268 articles with cancer registry data were identified with about 250 publications in 2022. The US SEER program currently produces over 1500 publications per year. The following main types of use were identified from the cancer registry laws: provision and use of aggregated and individual case data, contacting cancer patients from the registry population, and matching existing cohorts to the cancer registry. While aggregated and individual case data can usually be applied for using standardized forms, other types of use require standard scientific applications with an ethics vote and, if necessary, further approval. Selected practical examples show the different types of use. Conclusion The increasing number of publications is evidence of lively research use. Ne... Continued on ES/IODE ➡️ https://etcse.fr/hzBx ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Rose Fellows Series: Daniel Bustamante In this series, learn more about our Rose Traveling Fellowship awardees and the projects that they are working on. Daniel Bustamante, Ph.D., is a statistical geneticist and Postdoctoral Research Fellow at the Department of Epidemiology at Harvard T.H. Chan School of Public Health and affiliated Postdoctoral Scholar at the Broad Institute of MIT and Harvard, working under the mentorship of Karestan Koenen and co-mentored by Alicia Martin and Bizu Gelaye. Daniel’s work focuses on analyses of bipolar disorder, schizophrenia and posttraumatic stress disorder, in collaboration with researchers from Massachusetts General Hospital, Harvard Medical School, and abroad. Daniel is leading analyses of item level and underlying structure of these psychiatric traits and their polygenic risk in underrepresented populations, using blended genome-exome sequencing data from the Neuropsychiatric Genetics in African Populations (NeuroGAP) study, among other samples. - Tell us what your plans are for this project? The project includes visits to genomic and medical research sites (public psychiatric teaching hospitals and specialist clinics offering medical, diagnostic, out- and in-patient services) in Uganda and Kenya in early August, and Peru in mid-November of 2024. The fellowship objective is to expand my understanding of on-site psychiatric-genetics recruitment, data collection, clinical interviews and general health experiences in Uganda, Kenya, and Peru, in addition to meeting with local collaborators and research staff to discuss progress, protocols, analytic plans, and future directions. - What do you hope to gain? Through the fellowship, I hope to develop my relationships with local collaborators, enhance cross-cultural experiences, and deepen my understanding of field epidemiology recruitment efforts, protocols, and data collection, specific to these countries. The visits will help me to have first-hand exposure and understanding of factors that may affect individuals differently when seeking health-related services. Understanding these factors is crucial when working with psychiatric phenotypes, helping with interpretation of findings, and dissemination of results specific to underrepresented populations, such as those of African and admixed ancestries. Lastly, these outcomes just outlined are key components of the NIH K-award Career Development grant application I am writing, which aims to contribute to uncovering novel variants and examining the genetic risk for psychiatric phenotypes in traditionally underrepresented populations in genomic and medical studies. Learn more about the Rose Traveling Fellowship: https://lnkd.in/e-bSbNp5