Category Archives: Molecular Genetics

We didn't see any indication of their drinking coming back to baseline, so we think that maybe this epigenetic editing will produce a long-lasting effect, Pandey says. I think a lot more work needs to be done in terms of how this can be translated into humans for a therapy, but I have high hopes.

To test that the Arc gene was truly responsible for this outcome, the researchers also designed a Crispr injection meant to decrease its expression. They tested it in rats that werent exposed to alcohol in adolescence. Following the injection, the rats had more anxiety and consumed more alcohol than they did before.

The study raises the possibility that our molecular memory could be revisedor even erased. I'm struck deeply by this work showcasing the feasibility of changing a gene's memory of its experience, says Fyodor Urnov, a professor of genetics at the UC Berkeley and scientific director at the Innovative Genomics Institute of UC Berkeley and UC San Francisco. But, he continues, rats arent humans, and we shouldnt leap to conclusions. The distance between curing a rat and injecting a human being with addiction to alcohol with an epigenetic editor is a formidable one, says Urnov. I think that we are quite a ways away from somebody who has developed a mild drinking problem becoming eligible for a quick injection into their amygdala.

That said, Urnov, who is also the cofounder of Tune Therapeutics, an epigenetic editing company, could see an experimental therapy like this being tested among people with alcohol addiction who have relapsed from treatment several times and have no other therapeutic options left.

Yet, as with directly editing genes, there could be unintended consequences of tweaking their expression. Because Arc is a regulator gene involved in brain plasticity, modifying its expression could have effects beyond alcohol addiction. We don't know what other behaviors are altered by this change, says Betsy Ferguson, a professor of genetics at Oregon Health and Science University who studies epigenetic mechanisms in addiction and other psychiatric disorders. Its a balance between finding something that's effective and something that's not disruptive to everyday life.

Another complicating factor is that the expression of dozens, perhaps hundreds, of genes are altered by alcohol use over time. In people, it may not be as simple as turning up the expression of Arc, which is only one of them. While it may seem like the solution would be to tweak all of those genes, manipulating the expression of many at once could cause problems. Knowing that behaviors, including alcohol use behaviors, are regulated by a number of genes, it's really a challenging problem to solve, Ferguson says.

And its not clear how long the effects of such editing might last. Epigenetic changes that occur naturally can be temporary or permanent, says Ferguson. Some can even be passed onto future generations. Overall, she finds the idea of using epigenetic editing to treat alcohol addiction fascinating, but shed want to see the results replicated and the Crispr treatment tried in larger animals that more closely mimic humans.

That day may not be too far off, as a handful of companies have recently launched to commercialize epigenetic editing. At Navega Therapeutics, which is based in San Diego, researchers are studying how to treat chronic pain by turning down the expression of a gene called SCN9A. When its highly expressed, it sends out lots of pain signals. But it would be a bad idea to simply delete this gene, because some amount of pain is useful; it signals when something is going wrong within the body. (In rare cases, people with an SCN9A mutation that effectively renders it inactive are immune to pain, which makes them vulnerable to injuries they arent able to sense.) In experiments at Navega, epigenetic editing in mice seemed to repress pain for several months.

Urnovs Tune Therapeutics, meanwhile, plans to use epigenetic editing for a broad range of conditions, including cancer and genetic diseases. Though Urnov doesnt see epigenetic editing as the antidote to binge drinking, he thinks this proof-of-concept study shows that it may be possible to rewire our genes experiences to reverse some of the damage of early alcohol abuse. It is empowering, frankly, to consider the fact that we now have genome editing to fight a drugs pernicious action right at the venue where the drug inscribes its memories onto the brain, he says.

Read this article:
A New Kind of Genome Editing Is Here to Fine-Tune DNA - WIRED

Before trading their white coats for black gowns and receiving their degrees at Convocation Hall,several members of the Temerty Faculty of Medicine's Class of 2022 recently looked back on their time in med school and shared advice for future students.

Five of those students MD graduates Happy Inibhunu, Justin Lim and Jordi Klein,as well as MD/PhD gradsAlainna Jamal and Siraj Zahrdescribe the rollercoaster of emotions they felt during their education atthe University of Toronto, from delivering their first baby to losing their first patient.

Here is a snapshot of their reflections:

Graduating from: MD ProgramUp next: Residency in neurosurgery, Western University

Time goes by really fast, as sometimes I often rewind back to orientation and am amazed of the incredible friends I have made these last four years. Some highlights of my medical school journey are my first-ever triathlon, receiving an honorable mention by the Canadian Society of Palliative Care for my written piece, "10:30,providing care to patients throughout the COVID-19 pandemic through virtual and in-person means, and, undoubtedly, achieving my dream of becoming a neurosurgery resident.

These last four years in Toronto helped define the physician I aspire to be by building interdisciplinary and multidisciplinary networks in a harmonious manner, creating positive, empatheticand trustworthy rapport with patients, and having the extraordinary opportunity of striving diligently to provide care to neurosurgical patients as a life-long vocation.

Being part of the Class of 2022, which didmore than half of medical school during the pandemic, andnavigating clerkship within the pandemic was certainly a hard obstacle to overcome. Striving to build rapport and guidance with patients through the distance created with the application of Personal Protective Equipment (PPE) while balancing the uncertainty of the pandemic placed another layer of complexity to our learning. However, a defining characteristic that resonated through the pandemic is the ability to recognize, acknowledgeand strengthen virtues of humanity. For instance, sharing a laugh, providing extra time within visits, supporting one anotherand always remembering the person is separate from the disease. With this mindset, more unique aspects of clerkship and the pandemic shone through while building a harmonious community throughout my rotations among physicians, residents, allied health-care professionals, patients and caregivers.

I have been aspiring to this moment for a long time. To be one of the incoming PGY1 neurosurgery residents at Western University is a humbling honour. I am excited to continue on this path towards providing optimal care for patients, similar to my mentors, paving the way for me to soon become a well-rounded, skillfully trained neurosurgeon.

Advice for incoming students:It is often common to feel out-of-place in new situations, especially in medical school. You might hear of the phrase "imposter syndrome" in your first few weeks of orientation and throughout your career. Try not to be intimated by this phrase. Instead use it as a template to branch from. To get to where you are, it takes sacrifice, passionand excitement to dedicate your life to the betterment of others.

Graduating from: MD ProgramUp next: Residency in ObGyn, University of Toronto

I don't think I truly knew what I was getting myself into when I decided I wanted to become a physician.I just knew I wanted to contribute to my community in a meaningful way. Through the growing pains of medical school, I learned that there is something incredibly special about how our profession affords us the opportunity to be with people at some of their most vulnerable moments. The highs are high and the lows are low, but ultimately caring for others is central to what continues to draw me in to this profession.

Without a doubt, the most remarkable highlight of medical school has been watching my friends and classmates grow as people, as a communityand as future physicians and growing alongside them. It was so wonderful watching everyone comfortably settle into their future specialties this last stretch of medical school, and be truly excited about going into our respective clinical spaces.

Medical school has been filled with many firsts,which is what makes these four years so fulfilling and exciting, but so darn challenging at the same time. Navigating these firstskept me on my toes as I quickly learned that we all have things were good at (and things we're not so good at). It's funny remembering how nervous I was to take my first patient history. Now, that list of new experiences has grown exponentially all the way from delivering my first babyto experiencing my first patient death. Learning how to sit with these experiences will be something I will be working on for years to come.

I am extremely excited and nervous for the many upcoming milestones that come along with an ObGyn residency, and am really looking forward learning how to do things with my hands. I remember learning how to throw my first knot a few years ago, and it still hasn't hit me that soon enough I'll be learning how to operate.

Advice for incoming students:you will constantly feel like you dont have enough hours in a day.I remember feeling like I just did not ever have enough time. But I promise you that you do have time, and you will finish medical school excellent and competent.

The truth is, your to-do list will never end and the demands of medical school will feel overwhelming at times, but give yourself permission to do the things you need to do for you.

Jordi Klein

Graduating from: MD ProgramUp next: Residency in emergency medicine, University of Toronto

I became interested in medicine because of my own experiences as a patient, which led to an academic interest in co-design for health-care systems and institutions. Ive had some opportunities to use a co-design approach in creating lectures and resources for the MD program, and am excited to continue this work in residency. My experiences as a patient also cemented the importance of medicine as advocacy, and Im motivated to continue my advocacy work supporting the health-care needs of marginalized and under-represented communities.

Its true what they say:the days are long but the years are short.Med school was a collection of so many highlights. From de-stressing in the med lounge after an anatomy bellringer to delivering a baby for the first time, its amazing how much you grow in such a short amount of time. Among my greatest highlights were getting to know so many bright, hardworking, passionate future colleagues, who inspire me to be a better doctor and a better person.

I struggled a lot with imposter syndrome in medical school. I felt like I wasnt cut out to be a doctor, that I didnt belong here. It got worse in clerkship, as I would agonize over every little mistake, fearing it was evidence that all my worst fears were true and I actually wasnt good enough after all. Over the course of clerkship, my mentors helped me feel more grounded and learn to adopt a growth mindset. The imposter syndrome is still a work-in-progress but its become easier to see mistakes as opportunities to grow. Learn by failing!

Ive been incredibly lucky to have so many supportive mentors and colleagues throughout my training, and Im looking forward to having the opportunity to pay it forward by teaching, supportingand mentoring other learners here at U of T. My training would not have been the same without the residents who taught me procedures, got me coffee on night shifts, cried with me after patient deaths, coached me through tough daysand so much more. I hope to be that resident for future medical students.

Advice for incoming students:Each of you has something special to bring to this work. Dont be afraid to bring your full self into medical training. Let your strengths be your strengths, and find the people and places that help you feel like the best, most authentic version of yourself.

Graduating from: MD/PhD ProgramUp next: Residency in internal medicine, University of Toronto

I started my first research project as a bachelor of science student in 2010 under the skillful mentorship of Dr. S. Joseph Kim(an associate professor at the Institute of Health Policy, Management and Evaluation in the Dalla Lana School of Public Health)and Dr. Shahid Husain (a clinician investigator in the department of medicine in the Temerty Faculty of Medicine)in the multi-organ transplant program at Toronto General Hospital. They were the first to show me the physician-scientist career path, and I was fascinated.I saw research and clinical medicine as inextricably linked.I wanted to treat individual patients, while leading a research program that improves patient care and health-care systems.I am most interested in infectious diseases and epidemiology, particularly antibiotic resistance.

My research focuses on understanding transmission of antibiotic resistant bacteria in hospitals and communities, using epidemiological and genomic methods. These data allow us to make policy recommendations for infection prevention and control programs in Ontario.

The greatest highlight of my experience in the MD/PhD program was the opportunity tobe rigorously research-trained by my PhD supervisor, Dr. Allison McGeer [a professor in the Temerty Faculty of Medicine and Dalla Lana School of Public Health and clinician scientist at the Lunenfeld-Tanenbaum Research Institute at Sinai Health) as our team worked on new and evolving public health challenges (antibiotic resistance, and toward the end of my PhD, COVID-19). She is an authority in her field who also takes mentorship seriously.She gave me independence, while always offering constructive criticism and generous support.

I'm looking forward to honing my clinical skills and gaining independence as a physician, serving as a teacher and mentor to my junior peers, and answering the next question on my research agenda.

Advice for incoming students: Open doors for junior peers. Approach everything with a diversity, equityand inclusivity mindset.

Graduating from: MD/PhD ProgramUp next: Residency in anesthesiology, University of Toronto

Looking ahead, anesthesiology offers many avenues for scientific investigation as it encompasses the entire spectrum of medicine and surgery. Im interested in mechanisms of action of certain anesthetics on brain activity, as well as chronic pain mechanisms and treatment. The interplay between what we categorize as psychiatric/mental versus physical in chronic pain disordersand therapeutic modalities that target both is a particularly exciting area to me.

My main doctoral research under the supervision of Dr. Freda Miller [in the department of physiology] and Dr. David Kaplan [in the department of molecular genetics] revolved around how neurons are generated from neural stem cells to build the mammalian cortex. The cortex underlies our perception of sensory information, performance of motor activitiesand higher-order cognition, so you can imagine that aberrations in this process can lead to a whole host of disorders.

Honestly, my biggest highlight [of med school] would have to be meeting my wife, Tina Marvasti, who I couples matched with. Other highlights are the friendships Ive made and inspiring mentors I have met who have made me feel at home in Toronto.

I have faced many challenges, both academically and personally. Not to bore you with the details, but some useful things I have learned are that challenges are inevitable and necessary for growth, and that it is OK to lean on others for advice and guidance when youre stuck.

As I embark on the next phase of training, I look forward to developing focused clinical expertise and independence in managing patients of varying complexity and acuity. Im also looking forward tolearning from the fantastic clinical and scientific mentors in anesthesiology.

There is a proverb of unclear origin that goes: "The person who asks is a fool for five minutes, but the person who does not ask remains a fool forever. In medicine and science, you are faced with many unknowns or unfamiliar territory that naturally evoke fear. Ive noticed that there is sometimes a hidden pressure that even the most junior and inexperienced trainees need to always appear more certain and knowledgeable than is the case. So, in addition to the natural fears one has, there is an added pressure to behave with false certainty despite lack of experience. I think this really stunts learning and understanding, and is ultimately bad for patient care.

Advice for incoming students:Be humble, stay curious, maintain a growth mindset, and ask genuine questions if you dont understand something. Essentially, be willing to be a fool for a bit.

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Medical school grads reflect on their time at U of T and share tips for future students - University of Toronto

Enzyme research unlocks gateway for new medicines

CALS Early Achievement Award - Marcos Simoes-Costa

Former GGD student Cvic Innocent was named as a 2022 Woman in Optics by the International society for optics and photonics.

Advanced microscopy shines light on new CRISPR-Cas system

Cedric Feschotte publishes a study that reveals possible new coronavirus entry points in Cell Reports

E. coli bacteria offer path to improving photosynthesis

RNA analysis at heart of COVID-19 testing

Congratulations to Maureen Hanson - Elected to the American Academy of Arts and Sciences

Maureen Hanson is elected to the National Academy of Sciences

Jun "Kelly" Liu Recipient of the 2021 Robert A. and Donna B. Paul Academic Advising Award

Congratulations to Irma Fernandez - Recipient of the 2021 Graduate Diversity & InclusionExemplary Service Awards for Advanced Career Students

Emr wins $1.2M Shaw Prize in Life Science and Medicine

Pew scholar builds on gene-editing technology

Mann award winner unveils evolution, rules of gene expression

Originally posted here:
Welcome | Department of Molecular Biology and Genetics

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See the article here:
Genetic structure of Sclerotinia sclerotiorum populations from sunflower and cabbage in West Azarbaijan province of Iran | Scientific Reports -...

A team of researchers in Sweden gained new insights into the molecular mechanisms associated with plant reactions to environmental stressors, such as touching, pruning or infection.

The scientists explored the inner working of such reactions and the resulting behavior of the plant, discovering new crucial genetic factors which could impact crop yields.

The Lund University team reiterated that plants react to mechanical stimuli to better cope with specific environmental threats.

The study published in Science Advances explained that mechanical stimulation triggers rapid gene expression changes and affects plant appearance (thigmomorphogenesis) and flowering.

Thigmomorphogenesis is generated by repeated stimulation and includes significant modifications in the plant morphology, such as dwarfism, pithiness, altered mechanical properties of the stem, delayed flowering, improved anchorage strength of roots and reduced stomatal aperture.

Such changes tend to improve the ability of the plants to resist strong winds and improve their response to infection. In addition, these changes might strengthen resilience to cold, salinity, or drought.

The new research and afew other studies exploring similar plant reactions contribute to agrowing knowledge of mechanisms that scientists believe could be crucial to improving farming techniques.

Mechanostimulation has been gaining attention as apotential method for sustainable agriculture practices to improve food security, the researchers wrote.

However, the plant response to mechanical stimulation is very complex, as it depends on the intensity of mechanical load and frequency of exposures, they added. Understanding the molecular mechanism of plant mechanoperception and thigmomorphogenesis is imperative to apply this method for large-scale farming.

Previous research identified molecular mechanisms related to plant mechanoperception. Other studies noted the important relationship between jasmonic acid and touch signaling.

Despite many years of research on how transcriptional responses to mechanical stimulation in plants are controlled, only afew regulators have been identified and consistently validated, the researchers wrote.

Here, we used reverse genetics to further characterize the molecular mechanisms underlying touch signaling, they added.

For example, Olivier Van Aken, abiologist at Lund University, told ScienceAlert magazine: We exposed the plant thale cress to soft brushing, after which thousands of genes were activated, and stress hormones were released. We then used genetic screening to find the genes that were responsible for this process.

According to his colleague Essam Darwish, the study results solve ascientific mystery that has eluded the worlds molecular biologists for 30years.

We have identified acompletely new signaling pathway that controls aplants response to physical contact and touch, he added. Now the search for more paths continues.

The researchers believe that abetter understanding of those mechanisms might bring new opportunities for global agriculture, with climate change and conflicts threatening food security in many regions.

Given the extreme weather conditions and pathogen infections that climate change leads to, it is of utmost importance to find new ecologically responsible ways to improve crop productivity and resistance, Van Aken concluded.

Go here to see the original:
Studying Plant Reactions to Environmental Stressors Key to Sustainable Agriculture - Olive Oil Times

The New Indian Express (TNIE) had recently published a report which claimed that the Central Cultural Ministry is going to study Racial Purity of Indians. It talked about the Ministry of Culture looking forward to acquiring state-of-the-art DNA profiling kits and machines to trace the genetic history and trace the purity of races in India.

The Purity of Races angle in the article comes from the quote of Prof. Vasant Shinde, who serves as the adjunct professor at the National Institute of Advanced Studies in Bengaluru. Shinde notes that his team wants to study the mutation and mixing of genes that has happened in the last 10,000 years. While genetic mutation talks about the interaction of Indians with other populations of the world, studying the same will give us a clear-cut idea of our genetic history.

In the TNIE article, the news of the investigation to trace the genetic history of the Indian population was conflated with researchers studying the purity of races in India. While the concept of race remains purely a social concept and has no biological basis, purity here meant tracing the origins of DNA haplogroups among the Indian population. The deliberate contestation of the two led quite a stir among readers who were perplexed at the unscientific claims of the article. Soon, The Ministry of culture categorically dismissed the article as misleading.

However, it was for Congress MLA Rahul Gandhi to quote the report that was already labelled factually incorrect and to go on indirectly connect the dots with Hitlers racist policies in Nazi Germany. While tracing genetic ancestry had nothing to do with racial purity, Rahul Gandhi saw an opportunity to tag the article and score a political goal. By tagging the misleading piece from TNIE which could have sentimental repercussions and fan polarization in the society, Gandhi wrote on Twitter, The last time a country had a culture ministry studying racial purity, it didnt end well. India wants job security & economic prosperity, not racial purity, Prime Minister.

The Culture Ministry took note of the article in Morning Standard edition of TNIE on 28th May and termed it as misleading, mischievous and contrary to facts. The proposal is not related to establishing genetic history and trace the purity of races in India as alluded to in the article, it said. The statement noted that while the proposal by the Anthropological Survey of India (AnSI) is being examined under merits, it only deals with upgrading the existing DNA lab in Kolkata to next-generation sequencing facilities for certain ongoing projects.

Even after the Ministry of Culture dismissed the report for being factually incorrect, Rahul Gandhi went on to sensationalise the fake news to capitalise on the charged sentiment against the alleged research on racial purity. Central Minister for Culture, G Kishan Reddy lashed out at Gandhi in a tweet saying, Prior to Shri Gandhis tweet (probably from somewhere abroad), the Ministry of Culture, GoI had already flagged this article as misleading. Is he oblivious to this or has he intentionally chosen to further propagate such fake news?

Noted Genetic Scientist Neeraj Rai has lashed out at The New Indian Express for deliberatively publishing a misleading article. Describing the article as mischievous, he said he is upset about his research being described as studying racial purity. DNA research has great potential for improving our understanding of human health and history and should not be used to support discriminatory ideas, he added.

Rai, who heads the ancient DNA Lab at the Birbal Sahni Institute of Palaeosciences, Govt. of India, criticised Rahul Gandhi for his blatant attempt at politicising a scientific investigation. He wrote tagging Rahul Gandhi, Racial purity is not a thing and race is not a biologically supported context. It has been a tool for politicians to propagate racism and should not be conflated with genetic ancestry.

Author and economist Sanjeev Sanyal, who has written several books on Indian history and geography, has noted that this is a classic case of deliberately misleading a scientific study. Archaeo-genetics is a well-established field and attempts to trace the human journey. If anything it establishes that there is no such thing as pure race. Indeed, we are not even a pure species, he wrote.

Author and Scientist Anand Ranganathan, who teaches molecular biology at the Jawaharlal Nehru University asserted that Race is not a biological concept but a social one. Race is not a scientific concept, purity even less so. Not only are 8 Billion Humans 99.97% genetically identical, but the modern Human genome is also but a mishmash of primate, plant, bacterial, parasite, and viral DNA. he tweeted.

While the claims of the article and its purposeful politicization by Rahul Gandhi were criticised left, right and centre, this is not the only instance where a scientific study related to genetics was politicised. The Aryan Invasion Theory, which was used by Dravidian Politicians and leftist historians for decades to claim that the race of Aryans invaded/migrated to India between 2000 BCE and 1500 BCE, was debunked after new research proved that all claims of invasion by a white-skinned Aryan race have been without any scientific basis. DNA studies have established that not only do all people in the Indian subcontinent share a common ancestry, there have been migrations outwards from India, hinting at widespread trade and related migration.

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The New Indian Express uses the term racial purity to make false claims about research on genetic ancestry, Rahul Gandhi furthers the propaganda -...

The development of AI and large datasets will help automate the processes of drug discovery and development.

Science

by WangGuo on 31 May 2022

in Issue 1802

Drug discovery is a hard, time-consuming and expensive process. A single drugspends around 10 years in the lab before being released into the market. Furthermore, more than 99% of all the potential drugs end up unsuccessful. The rise of AI, as well as giant databases, seem to promise a new future in which drugs will be developed quicker, but will also be safer and more effective.

Before developing any drug, we need to find a biological site of interest that can be related to a disease. For example, GPCRs are cellular receptors that regulate cell proliferation and are involved in many cancers. Thus, creating drugs targeted at GPCRs is sensible and indeed, GPCRs are one of the main areas of research in our fight against cancer. The discovery of a potential biological site is challenging because sometimes we cannot characterise it entirely and/or delivering the drug to it would not be an easy task. This also means that we need to study many different biological sites, usually thousands of them through experiments, which takes up time and money. Using AI to run simulations of biological sites allows us to screen them much faster as we are not limited by how many experiments we can carry out.

Now that the drug target is identified, we need to actually develop our drug. Traditionally, this is done by humans through trial and error, but maybe in the future, computers could design the drug for us by analysing the structure of the biological site through simulations and dataset evaluation. Large and reliable datasets are essential for machine learning - the process by which computers learn from data as it allows for better performance, and so better and faster drug discovery. Precisely because the datasets must be large, these will arguably force labs and pharmaceutical companies around the world to share the data of their research with each other in order to increase the performance of computers in drug discovery. Could this make patents and IP obsolete? The traditional way of making money from pharmaceutical research would not be as effective as it is today. In that hypothetical future, the benefits of sharing your information are much greater than keeping it for yourself. There are two main types of data: sequence and imaging data. The first one is about the sequences of DNA, RNA and proteins, whereas the second is about structures of molecules/cells like proteins/mitochondria. There is another type of data that has the potential to revolutionise the way we understand genetics and drug discovery: epigenetic data, meaning the changes in gene activity caused by the environment. However, epigenetic data is very variable between individuals. Thus, the data is subject to particular interpretations and may not be easily storable.

Computers acquire information from these large datasets to integrate into their behaviour patterns to optimise their responses in a process called deep learning. The capability of deep learning is unbelievable. With it, computers can determine the structure of proteins by just reading their amino acid sequence. This is a milestone in molecular biology, as predicting how proteins fold has been impossible for humans to determine as there are too many factors to take into account.

Having said that, a world where all drugs are designed by computers is still far away. Even though there are many companies dedicated to this area of research and there are already functional prototypes, the pharmaceutical industry moves very slowly and mass-scaling a product is complicated not only due to logistics but also the necessity to guarantee high efficiency and safety.

To conclude, at present, there is a need for significant investment, in order to develop and commercialise drugs. Pharmaceutical companies and research institutions are under constant pressure to obtain more patents, which do not necessarily succeed in the goal of drugs: to improve peoples quality of life. Not only could computers dramatically accelerate the drug development process, but they might also democratise it by forcing organisations to make their data public.

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Computers will make our drugs in the future - FelixOnline

CUPERTINO, CA & DELRAY BEACH, Fla.--(BUSINESS WIRE)--OneCellDx and Genetics Institute of America announced today that they have signed a memorandum of understanding for a diagnostics commercialization agreement for the OneCellDx OncoPredikt HRD Assay. Genetics Institute of America will create a laboratory developed test (LDT) based on OneCellDxs proprietary AI Enabled Algorithm and assay. The OncoPredikt assay identifies Homologous Recombination Deficiency (HRD) in cancer patients with quicker turnaround times and lower costs.

Current HRD prediction tests are expensive, time-consuming, require multi-technique processes, and often have sample QC rejection due to low DNA quantity. OneCellDx has developed a proprietary AI-enabled tool to predict key genomic signatures. Genetics Institute of America will run a validation study in its CAP Accredited, CLIA certified facility and launch the laboratory developed test upon successful completion and acceptance of the study.

Our team of scientists and engineers have developed a uniquely impactful solution and are very excited to partner with the team at Genetics Institute of America in bringing OncoPredikt HRD to market, said Mohan Uttarwar, Co-founder and CEO of OneCellDx.

The ability to positively impact patients lives is one of the missions of Genetics Institute of America. Bringing the OncoPredikt HRD test to market will help in accelerating the development of novel pharmaceuticals, improving the care of thousands of patients, said Holly Magliochetti, CEO and Founder of Genetics Institute of America.

OneCellDx will present a poster session on OncoPredikt HRD at the American Society of Clinical Oncology Annual Meeting (ASCO), June 3-7, 2022, Chicago. Genetics Institute of America and OneCellDx will launch the LDT through HRD Pharma Development programs.

About OneCellDx

One Cell Diagnostics, Inc. is a genomics-based Precision Oncology Diagnostics company in Cupertino, CA. We have developed proprietary AI algorithms and leveraging AI and bioinformatics for developing first-in-class, clinically and analytically validated lab tests decoding actionable genetic alterations in individual tumors to help clinicians develop personalized treatment plans for patients. OneCellDx has developed two tests: OncoPredikt HRD - AI-enabled HRD prediction from H/E image, and OncoIndx - NGS-based comprehensive gene panel assays for multiple cancer types to identify key actionable biomarkers. For more information, please visit https://www.onecelldx.com/.

About Genetics Institute of America

Genetics Institute of America is a national high complexity molecular laboratory dedicated to heightening the awareness of early intervention and genetic testing to promote longevity and quality of life outcomes by focusing on DNA, RNA, and Proteins. Our modern CAP Accredited CLIA-certified laboratory facility in Delray Beach, FL, contains the most current technology, allowing us to provide leadership in both research and clinical laboratory testing. For more information, please visit http://www.GenLabUS.com/.

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OneCellDx and Genetics Institute of America Partner to Launch OncoPredikt HRD Assay - Business Wire

Summary: Study reports an overlap between genetic architecture and co-morbid mental health diagnosis. Researchers found 70% of the genetic signals associated with schizophrenia were also linked to bipolar disorder. Anorexia and OCD have a strong, shared genetic architecture.

Source: University of Colorado

More than half of people diagnosed with one psychiatric disorder will be diagnosed with a second or third in their lifetime. About a third have four or more.

This can make treatment challenging and leave patients feeling unlucky and discouraged.

But a sweeping new analysis of 11 majorpsychiatric disordersoffers new insight into why comorbidities are the norm, rather than the exception, when it comes to mental illness.

The study, published this week in the journalNature Genetics, found that while there is no gene or set of genes underlying risk for all of them, subsets of disordersincluding bipolar disorder and schizophrenia; anorexia nervosa and obsessive-compulsive disorder; andmajor depressionand anxietydo share a common genetic architecture.

Our findings confirm that high comorbidity across some disorders in part reflects overlapping pathways of genetic risk, said lead author Andrew Grotzinger, an assistant professor in the Department of Psychology and Neuroscience.

The finding could ultimately open the door to treatments that address multiple psychiatric disorders at once and help reshape the way diagnoses are given, he said.

If you had a cold, you wouldnt want to be diagnosed with coughing disorder, sneezing disorder and aching joints disorder, Grotzinger said.

This study is a stepping stone toward creating a diagnostic manual that better maps on to what is actually happening biologically.

How the study worked

For the study, Grotzinger and colleagues at University of Texas at Austin, Vrije Universiteit Amsterdam and other collaborating institutions analyzed publicly available genome-wide association (GWAS) data from hundreds of thousands of people who submittedgenetic materialto large-scale datasets, such as the UK Biobank and the Psychiatric Genomics Consortium.

They looked at genes associated with 11 disorders, including: schizophrenia, bipolar disorder,major depressive disorder, anxiety disorder, anorexia nervosa, obsessive-compulsive disorder, Tourette syndrome, post-traumatic stress disorder, problematic alcohol use, ADHD and autism.

In addition, they looked at data gathered via wearable movement tracking devices, and survey data documenting physical and behavioral traits.

Then they applied novel statistical genetic methods to identify common patterns across disorders.

Linked diagnoses

They found 70% of the genetic signal associated with schizophrenia is also associated with bipolar disorder. That finding was surprising as, under current diagnostic guidelines, clinicians typically will not diagnose an individual with both.

They also found anorexia nervosa andobsessive-compulsive disorderhave a strong, shared genetic architecture, and that people with a genetic predisposition to have a smaller body type or low BMI (body mass index), also tend to have agenetic predispositionto these disorders.

Not surprisingly, as the two diagnoses often go together, the study found a large genetic overlap between anxiety disorder and major depressive disorder.

When analyzing accelerometer data, the researchers found disorders that tend to cluster together also tend to share genes that influence how and when we move around during the day.

For instance, those with internalizing disorders, such as anxiety and depression, tend to have a genetic architecture associated with low movement throughout the day.

Compulsive disorders (OCD, anorexia) tend to correlate with genes associated with higher movement throughout the day, and psychotic disorders (schizophrenia and bipolar disorder) tend to genetically correlate with excess movement in the early morning hours.

When you think about it, it makes sense, said Grotzinger, noting that depressed individuals often present as fatigued or low energy, while those with compulsive disorders can have difficulty sitting still.

In all, the study identifies 152 genetic variants shared across multiple disorders, including those already known to influence certain types of brain cells.

For instance, gene variants that influence excitatory and GABAergic brain neuronswhich are involved in critical signaling pathways in the brainappear to strongly underlie the genetic signal that is shared across schizophrenia andbipolar disorder.

Whats next

While much more needs to be done to determine exactly what the identified genes do, Grotzinger sees the research as a first step toward developing therapies that can address multiple disorders with one treatment.

People are more likely today to be prescribed multiple medications intended to treat multiple diagnoses and in some instances those medicines can have side effects, he said.

By identifying what is shared across these issues, we can hopefully come up with ways to target them in a different way that doesnt require four separate pills or four separate psychotherapy interventions.

Meantime, just understanding the genetics underlying their disorders may provide comfort to some.

Its important for people to know they didnt just get a terrible roll of the dice in lifethat they are not facing multiple different issues but rather one set of risk factors bleeding into them all.

Author: Press OfficeSource: University of ColoradoContact: Press Office University of ColoradoImage: The image is in the public domain

Original Research: Open access.Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis by Andrew D. Grotzinger et al. Nature Genetics

Abstract

Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis

We interrogate the joint genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis.

We identify four broad factors (neurodevelopmental, compulsive, psychotic and internalizing) that underlie genetic correlations among the disorders and test whether these factors adequately explain their genetic correlations with biobehavioral traits.

We introduce stratified genomic structural equation modeling, which we use to identify gene sets that disproportionately contribute to genetic risk sharing. This includes protein-truncating variant-intolerant genes expressed in excitatory and GABAergic brain cells that are enriched for genetic overlap across disorders with psychotic features.

Multivariate association analyses detect 152 (20 new) independent loci that act on the individual factors and identify nine loci that act heterogeneously across disorders within a factor.

Despite moderate-to-high genetic correlations across all 11 disorders, we find little utility of a single dimension of genetic risk across psychiatric disorders either at the level of biobehavioral correlates or at the level of individual variants.

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Multiple Diagnoses Are the Norm With Mental Illness and a New Genetic Study Explains Why - Neuroscience News

image:Children with Joubert Syndrome, like the girl in the image, may face a brighter future if hippocampal defects can be addressed. view more

Credit: JSUK

An important link has been found between the intellectual disability experienced by children with the rare disease Joubert Syndrome (JS) and defects in the hippocampus. The hippocampus is the part of the brain associated with learning and memory. It also plays a role in various neurological and psychiatric disorders.

Biologists at the University of Bath in the UK, led byDr Vasanta Subramanian,made this link in animal models by manipulating a gene (one of 34) known to cause JS in humans. Results fromthe studyare published inHuman Molecular Genetics.

By creating a deletion in the gene Talpid3 in healthy mice, graduate student Andrew L Bashford found that animals went on to develop defects to the primary cilia a cell structure that is essential in the development of the hippocampus. When examining the brains of mutant animals, the researchers observed defects in the hippocampus that bore a striking resemblance to those found in children with JS.

The primary cilia long, thin organelles that protrude from the surface of most cells work like cellular antennae, sending signals from the external environment of the cell to the interior, instructing the cell on how to behave (e.g. should it migrate, divide, stop dividing?). Primary cilia are important for the structure and function of many types of cells, including brain cells.

The findings from the study suggest a link between hippocampal defects, and the learning and memory deficits seen in JS patients. Malformations in the hindbrain (the lower part of the brainstem) are already known to be responsible for many of the physical symptoms associated with JS.

This is the first time we have seen a link between changes to the hippocampus and this disease in mouse models, said Dr Subramanian. This is an exciting area of research that we hope to continue making a contribution to. Joubert Syndrome is one of many rare diseases that has a devastating impact on those affected and is now rightly getting the research attention it deserves.

With further research on animal models, Dr Subramanian and her team expect to deepen their understanding of the causes of JS. In time, they hope drugs will be developed to target some of the genes or proteins involved in the disease, thereby alleviating symptoms or stopping the disease from developing in the first place.

Joubert Syndrome is a rare childhood disease that leads to poor muscle coordination, developmental delay, abnormal eye movements and neonatal breathing abnormalities. It is estimated that between 1 in 80,000 and 1 in 100,000 newborns are affected by the condition.

Speaking on behalf of the family-support organisation Joubert Syndrome UK, Faith Douthwaite said: We are delighted to hear about this new research, and also appreciate the dedication of medical professionals who continue to unravel the mysteries of Joubert Syndrome so as to improve the health and wellbeing of our beautiful and unique children.

Human Molecular Genetics

Experimental study

Animals

Hippocampal neurogenesis is impaired in mice with a deletion in the coiled coil domain of Talpid3-implications for Joubert Syndrome

26-Apr-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Joubert Syndrome: the link between intellectual disability and defects in the hippocampus - EurekAlert