Category Archives: Transhuman News

Scientists at the University of Virginia (UVA) School of Medicine have developed a promising gene therapy to target the mutation behind a severe form of epilepsy.

The new Dravet syndrome treatment could help improve and extend the lives of people with the rare but debilitating disease.

The challenge: People born with Dravet syndrome start experiencing seizures when theyre still infants. Seizures continue throughout their lives and often lead to a host of health problems severe developmental delays, speech impairments, intellectual disability, and movement difficulties.

There is no cure for Dravet syndrome, and 10-20% of children born with it die before reaching adulthood.

Certain diets, medications, and therapies can help reduce the frequency and severity of seizures, but patients still require constant, lifelong care.

Between 10% and 20% of children born with Dravet syndome die before reaching adulthood.

The idea: In more than 80% of cases, people with Dravet syndrome have a mutation in a particular gene (called SCN1A) that results in reduced production of a critical protein in the brain.

This leads to a shortage of that protein in specialized brain cells, called interneurons, that protect against seizures.

No existing Dravet syndrome treatment directly addresses the underlying cause of the disease so the UVA team decided to make one that does.

The Dravet syndrome treatment: Dravet is usually caused by a single random mutation, but people generally carry two copies of every gene. The researchers aimed to use the second intact gene to treat the disease.

The treatment completely prevented seizures and premature death in infant mouse models of Dravet.

Using an approach they call Targeted Augmentation of Nuclear Gene Output (TANGO), the scientists developed a Dravet syndrome treatment that prompts the intact gene to increase protein production.

When tested in mouse models of Dravet syndrome, the treatment completely prevented seizures and premature death in infant mice.

The animals interneurons were more responsive, more active, and better able to do their jobs, according to a press release.

The big picture: Therapies that work in mice often fail in humans, but early results in human trials suggest this Dravet syndrome treatment has a shot.

More than 70% of children with Dravet in an ongoing phase 1/2A study experienced a reduction in seizure frequency following treatment, according to Stokes Therapeutics, the company developing the drug.

That study was small, with just 21 participants so far, and these are interim results, so its still too early to say whether the therapy (called STK-001) will ultimately make it to patients.

Still, if the results hold up in larger trials, the new treatment could help people with Dravet syndrome live longer, healthier lives.

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Gene therapy shows promise at treating severe form of epilepsy - Freethink

Shares of Mustang Biohave fallen more than 13% in premarket trading after the company announced the U.S. Food and Drug Administration had placed a hold on the companys Investigational New Drug application for its bubble boy gene therapy.

The Worcester, Mass.-based company said the regulatory agency placed a hold on the planned Phase II study pending Chemistry, Manufacturing and Controls (CMC) clearance for MB-207, Mustangs lentiviral gene therapy. Mustang intended to initiate a pivotal Phase II study to assess the gene therapys safety, tolerability, and efficacy as a potential treatment forX-linked severe combined immunodeficiency (XSCID), also known as bubble boy disease. The study would include patients who have been previously treated with a hematopoietic stem cell transplantation.

MB-207 has previously been granted Orphan Drug and Rare Pediatric Disease designations by the FDA, makingthe asset eligible for a rare pediatric disease voucher.

In addition to the planned MB-207 Phase II study, Mustang is conducting a Phase I/II XSCID study in newly diagnosed infants under the age of two with MB-107. Like MB-207, MB-107 has also been granted Rare Pediatric Disease, Orphan Drug and Regenerative Medicine Advanced Therapy designations.

Manuel Litchman, M.D., president and chief executive officer of Mustang Bio, said the company hopes to efficiently expedite the development of both MB-2017 and MB-107. He said they believe they are well positioned to address the FDAs CMC concerns.

While Mustangs gene therapy trial is temporarily prohibited from the beginning, the FDA did clear several other companies requests to begin clinical studies.

Mind Medicines LSD Formulation Moves into Phase IIb

New York-based Mind Medicines IND for a Phase IIb study of MM-120 for treatinggeneralized anxiety disorder (GAD) was given the go-ahead by the FDA. That trial had been on hold,but the hold was recently lifted after Mind Medicines address of participant monitoring protocols for the upcoming study. The Phase IIb trial is expected to begin later this year.

The company expects to enroll a total of 200 participants who will receive a single administration of up to 200 g of MM-120 or placebo. The study's primary endpoint is the reduction in anxiety symptoms for up to 12 weeks following a single administration of MM-120, a pharmacologically optimized form of LSD.

Imara Inc. Will Begin Cardiac Study in Second Quarter

Bostons Imara Inc. will begin assessing tovinontrine (IMR-687) in a Phase II studyto treatheart failure with preserved ejection fraction (HFpEF). The clinical trial is expected to begin in the second quarter of 2022. The trial will evaluate tovinontrine in approximately 170 patients 45 years of age or older with persistent HFpEF symptoms. The primary endpoint of the study will be change in NT-proBNP, with secondary endpoints that include safety and tolerability and the quality of life measures.

Tovinontrineis a highly selective and potent small-molecule inhibitor of phosphodiesterase-9 (PDE9).

Nanoscope Therapeutics Heads into Phase II with Stargardt Therapy

Texas-based Nanoscope received IND clearance from the FDA for a Phase II study of its Multi-Characteristic Opsin (MCO-010) ambient-light activatable optogenetic monotherapy. MC)-010 is being assessed as a gene therapy to restore vision in Stargardt patients. Stargardt, an inherited retinal disease, is a form of macular degeneration affecting children and adults.

Nanoscopes MCO-010 gene therapy reprograms healthy retinal cells to make them photosensitive. It uses proprietary AAV2 vectors. The Phase II trial is expected to begin in the first half of 2022.

Nanoscope is currently conducting a PhaseIIbstudy of MCO-010 for retinal pigmentosa (RP) patients. MCO-010 has received orphan drug designations from the FDA for RP and Stargardt.

SwanBio Takes Rare Disease Gene Therapy into the Clinic

Philadelphia-based SwanBiosgene therapy for the treatment of adrenomyeloneuropathy (AMN) has been cleared for a Phase I/II study. SwanBios lead candidate SBT101 is the first AAV-based gene therapy in development designed to compensate for the disease-causing ABCD1 mutation in AMN patients.

Adrenomyeloneuropathy is the adult-onset degenerative spinal cord disease that affects people with adrenoleukodystrophy, a rare, genetic and metabolic condition. The Phase I/II study will assess the safety and efficacy of the gene therapy. It is expected to begin in the second half of 2022.

Preclinical data shows that treatment with SBT101 demonstrated dose-dependent improvement of AMN disease markers in animal models. The gene therapy was also well-tolerated in non-human primates at six months post-treatment. The company said the SBT101 program builds on its ongoing natural history study of AMN.

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FDA Pulls on the Reins for Mustang's Gene Therapy as Others Advance - BioSpace

image:The Blood Proteoform Atlas (BPA) compiles ~56,000 proteoforms identified from 21 human cells types and plasma view more

Credit: Please credit Kelleher and Levitsky labs at Northwestern University

Northwestern University scientist have discovered families of proteins in the body that could potentially predict which patients may reject a new organ transplant, helping inform decisions about care.

The advancement marks the beginning of a new era for more precise study of proteins in specific cells.

Scientists tend to look at shifting patterns of proteins as if through goggles underwater, taking in just a fraction of available information about their unique structures. But in a new study to be published January 27 in the journal Science, scientists took a magnifying glass to these same structures and created a clarified map of protein families. They then held the map up in front of liver transplant recipients and found new indicators in immune cell proteins that changed with rejection.

The result, the Blood Proteoform Atlas (BPA), outlines more than 56,000 exact protein molecules (called proteoforms) as they appear in 21 different cell types almost 10 times more of these structures than appeared in similar previous studies.

Scratching the surface of potential

Were working to create the protein equivalent of the Human Genome Project, said Neil Kelleher, a leading expert in proteomics and co-corresponding author of the paper. The BPA is a microcosm of that, including a specific-use case.

Kelleher is the Walter and Mary Glass Professor of Molecular Biosciences and professor of chemistry in NorthwesternsWeinberg College of Arts and Sciencesand a professor of medicine inNorthwestern University Feinberg School of Medicine.He is also the director of theChemistry of Life Processes Institute(CLP) and faculty director ofNorthwestern Proteomics, a center of excellence within CLP that develops novel platforms for drug discovery and diagnostics.

Each human gene has at least 15 to 20 unique forms of processed proteins (proteoforms). And with 20,300 individual genes in the human body, there are millions of proteoforms created by genetic variation, modification or splicing. Kelleher said with a complete roadmap of each genes family of proteinsthe goal of a major science initiative known as the Human Proteoform Project discoveries about disease, aging and new therapeutics will accelerate.

The Kelleher lab uses state-of-the-art mass spectrometry and data analysis to identify proteofoms in cells and blood efficiently, keeping proteoforms intact in a form of top-down analysis rather than cutting them up into tiny pieces as with the industry standard.

Were starting to see the complexity, he said. In this paper, we demonstrate patient-, cell type- and proteoform-specific measurements, which allows us to get to better biomarkers.

A blood test for liver transplant rejection

Having team members across disciplines allows the project to conceptualize a move from lab bench to bedside. As Kelleher probes the scientific basis for phenomena in the cell, co-corresponding author and Northwestern Medicine transplant hepatologist Josh Levitsky works with him to understand how these could be applied to a specific system.

Levitsky, professor of medicine, surgery and medical education at Feinberg, originally connected with Kelleher through his leadership in the biomarkers space, in which measurable signs in the blood are used to predict health metrics in patients facing disorders and in this instance, liver transplant rejection.

It was really important for Neil that there was a biologically relevant example to contextualize how these proteoform panels can identify diseases non-invasively as markers, Levitsky said. And theres also a need in my field to have mechanistic biomarkers that are more relevant to their immune biological pathways. This could be the start of a new era in cell-specific markers.

Physicians must suppress the immune system with drug therapy and monitor liver transplant recipients for signs of rejection, often only responding after an episode has begun. Guesswork throughout this process could be eliminated with specific knowledge about whats happening at the most granular level.

With the BPA as a reference map, the team took blood samples from participants in one of Levitskys biomarker collection studies. They examined which proteoforms seemed to activate in response to the transplant and identified those that changed compared to patients without rejection.

Next, the Levitsky and Kelleher team developed a panel of 24 proteoforms from the initial study and looked at them in transplant recipient samples from across the country. They found the same proteoforms lit up as in the first trial.

Moving the field forward

The promise here is to be able to use this panel moving forward to be able to identify patients who have no signs of rejection versus those who have very early evidence of rejection, Levitsky said. If we can pick up on this several weeks before rejection actually happens, we might be able to modify immunosuppression.

Levitsky continues to examine how proteoforms change in transplant recipients over time to develop additional biomarkers that may inform how he treats patients down the line. Kelleher said as the number of cell types in the atlas grows, so too will potential ways to use it. In addition to broadening understandings of human biology, the BPA could have similar applications across immune disorders.

The study, The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells, was conducted across six institutions with 26 scientists. Rafael D. Melani, a research assistant professor in the Kelleher Group, was the first author of the paper, along with Vincent R. Gerbasi, also from Northwestern, and Lissa C. Anderson from Florida State University.

The research was supported by the National Institute of General Medical Sciences of the National Institutes of Health (award numbers: P41 GM107569, R21LM013097, T32 GM105538 and R21 AI135827), the Human Biomolecular Atlas Program (award number: UH3 CA246635-02), Paul G. Allen Frontiers Program Award (award number 11715), the Knut and Alice Wallenberg Foundation grant (2016.0204) and the Swedish Research Council grant (2017-05327). Work performed at the National High Magnetic Field Laboratory is supported by the National Science Foundation Division of Materials Research and Division of Chemistry and the State of Florida.

The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells

28-Jan-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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Researchers identify proteins that could predict liver transplant rejection - EurekAlert

A Phase 2 trial can begin investigations on MCO-010 gene therapy as treatment for patients with Stargardt disease. The multi-characteristic opsin ambient-light activatable optogenetic monotherapy may restore vision in patients with this rare macular degeneration.

The developer of MCO-010, Nanoscope Therapeutics Inc, announced that it received investigational new drug (IND) clearance from the US Food and Drug Administration (FDA).

The trial is expected to start in H1-2022. MCO-010 is designated as an orphan drug by the FDA for Stargardt disease and retinitis pigmentosa (RP).

The clincal-stage biotechnology company is currently conducting a Phase 2b multicenter, randomized, sham-controlled, double-masked study of MCO-010 for patients with retinitis pigmentosa.

Retinitis pigmentosa is a group of rare, genetic disorders associated with difficulty seeing at night and the inability to see peripherally due to the breakdown and loss of cells in the retina.

Stargardt is an inherited rare disease that affects children and adults. As a result of this retinal disease, photoreceptors in the eye degenerate. MCO-010 gene therapy makes them photosensitive by reprogramming the healthy retinal cells.

MCO-010 is a single intravitreal injection administered in a medical office setting. Proprietary AAV2 vectors deliver the MCO genes to the cells where they express polychromatic opsins and enable vision.

Patients with Stargardt and retinitis pigmentosa can utilize this therapy regardless of underlying gene mutations.

"Presently allexisting trialsattemptto slow down the progressionof vision loss in patients with Stargardt disease, Optogenetic approach is to restore vision. Thiscan bea groundbreaking attempt to evaluate optogenetic gene therapyto improve vision inStargardt patients. I'm excited by the potential MCO-010 has to restore vision for many patients with sight loss caused by outer retinal dystrophies including dry age-related macular degeneration," David Boyer, MD, Retina-Vitreous Associates Medical Group, adjunct clinical professor of ophthalmology, Keck School of Medicine, University of Southern California said in a statement.

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FDA Clears MCO-010 Gene Therapy as IND for Stargardt Macular Degeneration - MD Magazine

BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)--EdiGene, Inc., a global biotechnology company focused on translating gene-editing technologies into transformative therapies for patients with serious genetic diseases and cancer, announced a research and development collaboration with Haihe Laboratory of Cell Ecosystem to develop hematopoietic stem cell regenerative therapies and platform technology by combining resources and expertise from both sides.

The Haihe Laboratory of Cell Ecosystem, run by the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, is focused on conducting fundamental research, innovation, and translation in the cell ecosystem.

Under the agreement, both parties will jointly develop hematopoietic stem cell regenerative therapies, including the development of innovative genetically-modified hematopoietic stem cell therapies and the exploration of novel biomarkers to optimize quality control for stem cell production.

With top-notch resources and industry-university-research cooperation, well facilitate the development of cell-based medicine and therapies, said Professor Tao Cheng, Deputy Director of Haihe Laboratory of Cell Ecosystem and President of the Institute of Hematology and Blood Diseases Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College, a leading hematology researcher who has made a series of discoveries relating to the regulatory and regenerative mechanisms of hematopoietic stem cells. Hematopoietic stem cells (HSCs) have the potential for long-term self-renewal and can differentiate into various types of mature blood cells. These stem cells can be harnessed to provide treatment for a broad range of diseases such as hematological tumors, autoimmune diseases, and hereditary blood disorders. We believe that this collaboration with EdiGene will accelerate the innovation and translation in the field of HSCs, thus enabling healthier patients with new therapies."

Professor Cheng was awarded the second prize of the National Natural Science Award 2020 as the first author of work on basic and translational research that advanced the development of adult hematopoietic stem cells for therapeutic applications.

EdiGene is scaling up clinical translation and development of the first gene-editing hematopoietic stem cell therapy in China following the 2021 approval by the China National Medical Products Administration its IND for its investigational therapy ET-01. Our team has extensive experience in the development and translation of cutting-edge technologies including hematopoietic stem cell and gene editing, said Dong Wei, Ph.D., CEO of EdiGene. "This collaboration with Haihe Laboratory of Cell Ecosystem will further our exploration in the field of hematopoietic stem cells. The partnership with this leading academic institute and our translational know-how enable us to move forward in bringing more innovative treatment options to patients in China and around the world.

In 2021, EdiGene initiated a Phase I multicenter clinical trial of ET-01, its gene-editing hematopoietic stem cell therapy for transfusion-dependent -thalassemia. EdiGene has enrolled the first patient at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Currently, the clinical trial is being conducted in Tianjin and Guangdong-Hong Kong-Macao Greater Bay Area (Greater Bay Area). EdiGene also presented its latest research on new surface markers and migration of hematopoietic stem cells at the 63rd Annual Meeting of the American Society of Hematology (ASH) in 2021.

About Haihe Laboratory of Cell Ecosystem

The Haihe Laboratory of Cell Ecosystem ("the Laboratory"), run by the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, is one of the five registered Haihe Laboratories approved by Tianjin Municipal People's Government. With the goal of promoting population health with cell ecosystem, the Laboratory adheres to developing technological frontier, enhancing peoples health, and promoting research, innovation, and development of cell ecosystem in five key areas: cellular ecosystem, cellular ecology and immunity, cellular ecological imbalance and major diseases, cellular ecological reconstruction and frontier technology of cellular ecological research.

About Institute of Hematology and Blood Diseases Hospital (IH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS/PUMC)

Founded in 1957, IH is a tertiary specialty hospital under the National Health Commission of China and is the supporting unit of the National Clinical Research Center of Hematologic Diseases and the State Key Laboratory of Experimental Hematology. It is also the main founding unit of Tianjin Base, the core base of the Chinese medical science and technology innovation system with the goal of becoming "the innovation hub of hematology in China." IH mainly engages in basic research, applied research, clinical diagnosis and treatment of hematological diseases, standard-setting, new technology research, new drug evaluation, and translation in hematology and related fields. IH is leading in the diagnosis and treatment of hematological diseases in China and a global scale and has made original achievements. Since 2010, IH has been awarded first place in the Hospital Specialty Reputation Ranking (Hematology) for 12 consecutive years. It has won first place in the Hematology Specialty Ranking for ten consecutive years since 2010 and ranked the first in hematology by the Scientific and Technological Evaluation Metrics (STEM) for Chinese hospitals for eight consecutive years since 2014.

About EdiGene, Inc

EdiGene is a global, clinical-stage biotechnology company focused on translating gene editing technologies into transformative therapies for patients with serious genetic diseases and cancer. The company has established its proprietary ex vivo genome-editing platforms for hematopoietic stem cells and T cells, in vivo therapeutic platform based on RNA base editing, and high-throughput genome-editing screening to discover novel targeted therapies. Founded in 2015, EdiGene is headquartered in Beijing, with offices in Guangzhou and Shanghai, China and Cambridge, Massachusetts, USA. More information can be found at http://www.EdiGene.com.

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EdiGene Enters Strategic R&D Collaboration with Haihe Laboratory of Cell Ecosystem to Develop Hematopoietic Stem Cell Regenerative Therapies and...

The 2021 Nobel Prize in physiology or medicine was awarded to David Julius and Ardem Patapoutian for their discoveries of receptors that sense temperature and pressure, work that exemplifies how difficult research can be. Through hundreds of mice, tens of thousands of cells and millions of bacterial colonies, the research groups that made the winning discoveries persisted in asking important questions about how the brain detects its surroundings.

Researchers in Julius and Patapoutians labs who made key discoveries at the bench worked through many technical problems and disappointments in pursuit of the molecules behind sensation. The Secret History of Touch tells five stories of their persistence. Here is the fourth.

COURTESY OF THE NOBEL FOUNDATION

A schematic shows how Bertrand Coste used patch-clamp electrophysiology to discover piezo1, applying a mechanical force to a cell while also measuring current (top line). Later experiments showed that the protein is a channel that opens in response to mechanical forces against a nearby membrane.

In the mid-2000s, Ardem Patapoutian, known for his studies of temperature sensitive ion channels called TRPs, wanted to transition into studying mechanotransduction.

Patapoutian did not have time for an interview for this story, but in an email, he wrote, After studying temperature sensation for 10 years, it was a natural transition to ask how mechanical force is sensed.

Like the search for the cold receptor, it was another risky question, fraught with the possibility of failure. Sanjeev Ranade, who joined Patapoutians lab as a graduate student to study thermosensation, said, Many labs had been looking for the identity of the gene or genes that allow us to sense touch. Many labs were not successful in finding these genes.

Courtesy of the Nobel Foundation

A schematic shows how Bertrand Coste used patch-clamp electrophysiology to discover piezo1, applying a mechanical force to a cell while also measuring current (top line). Later experiments showed that the protein is a channel that opens in response to mechanical forces against a nearby membrane.

So when physiologist Bertrand Coste joined the lab as a postdoc to search for the protein that lets human neurons sense pressure, Ranade said, It was one of those almost I cant believe youre doing this kind of projects.

Like Makoto Tominaga in David Julius lab, Coste was an experienced electrophysiologist who came to a new lab in California with a reputation for receptor hunting and immediately began to build a new electrophysiology rig. He had studied mechanosensory neurons as a graduate student and was skilled at recording from a neuron with an electrode while gently prodding it with a tiny glass probe a technique that few others in the world used.

Recording these mechanically activated currents naturally pushed me to the question of what are the ion channels that are involved in this activity, Coste said. Patapoutians lab, which lately had cloned TRPA1 and TRPM8, struck him as the ideal environment to try to answer the question.

Coste initially planned to sift through the DRG to find neurons that respond to mechanostimulation and then extract their RNA and screen for the genes governing pressure sensation. But pilot experiments made it clear that the strategy was impractical. So he took a different approach: He tested as many cell lines as he could lay hands on, looking for one that would respond to pressure by depolarizing. With immortalized cell lines you have endless materials, he said. Its easy to use, and every cell is a clone of the other cells.

Scripps Research Institute

From left, Bertrand Coste, Ardem Patapoutian, Bailong Xiao and Seung Eun Kim when Coste and Xiaos paper and Kims paper were published together in Nature in 2012.

Coste found a neuroblastoma line that fit the bill and winnowed down its list of highly expressed genes to the most interesting candidates: transmembrane proteins with unknown function that shared some characteristics with ion channels.

That left a list of dozens of genes. Coste began to use siRNA to knock them down one at a time and then prodded the altered cells, watching for one that would fail to respond to mechanical stimulation. Electrophysiology is highly reliable but also very slow. He averaged about two candidate genes a week, and, for a year or more, every single candidate he tested had no effect on the cells response. Not making progress can be tough. A few months in, after many trials and no success, Coste said, My mood was declining very fast.

We are scientists. We like to think, to problem solve, he said. While planning the screen and working around the technical issues, hed had a chance to solve problems. But the screen itself was very repetitive. Coste brought the problem to Patapoutian, explaining that even though he was excited about the possible results of the project, the mindless grind of doing the same experiment over and over again and getting no result was difficult. Patapoutian, according to Coste, was understanding; he assigned a technician to help and suggested a second, more tractable project he could work at on the side. I was relieved of doing every day the same thing, every day having negative results, Coste said.

Scripps Research Institute

A structure of the piezo channel

Finally, after ruling out 72 candidate genes, Coste found an siRNA that blunted the cells response to mechanical stimulation. Ranade said, They could have easily quit at 72, and said, OK, its been a year, we have nothing. And yet, they found it at 73.

The gene was mysterious, but it was large, with an estimated 24 to 36 transmembrane domains. Besides controlling the neuroblastoma cells mechanical response, when cloned into mechanically inert cells, it made them sensitive. The team dubbed it Piezo, after the Greek word for pressure, and soon found that mice have two closely related Piezo proteins.

Coste said characterizing the channel was exhilarating: After one year of screening every experiment you do is telling you something interesting on the activity of this channel.

Coste and many colleagues in the Patapoutian lab would go on to show that Piezo1 and Piezo2 play integral roles in mammals sense of touch and many other physiological functions. Even before that, Ranade said, it was clear that the finding was important. Every single one of us in the lab, when Bertrand found Piezos, we all kind of knew that he struck gold.

What keeps researchers going through failure after failure? ASBMB Today asked psychologist Ayelet Fishbach, who studies motivation, work and learning from failure.

Fishbach and colleagues recently published a study investigating work-related one-time failures. After taking a two-option multiple choice quiz, Fishbach and colleagues found, participants who had received negative feedback performed worse on a follow-up quiz than those who had received positive feedback.

Although the study investigated one-time failure to guess an insignificant piece of information rather than the longer and more fraught process of research, Fishbach said that its conclusions reflect her own experience as a researcher and mentor.

There are two categories of problems with learning from failure, she said. Cognitively, it can be harder to learn from the unexpected than the expected and more difficult to seek out the reasons that a hypothesis missed the mark than to accept that it was correct. Getting people to pay attention to what didnt work is notoriously hard, she said.

The second category is emotional. It is easier to ignore a failure than to engage with it. And sometimes people especially those with relatively little expertise in a field learn the wrong lesson from failure, concluding that they are unable to execute the task at hand. Whats more, Fishbach said, Doing something with no sense of progress is psychologically hard. You can tell yourself that one day it will pay off, but its not today or yesterday or tomorrow. And people give up.

Much like David Julius, Fischbach said that social support, encouraging words and help with troubleshooting from others can help keep people motivated. But, Julius pointed out, Its not just me. They have to have their own gyroscope. He added that there are times when he has doubted the future of a project and has gotten inspiration from persistent trainees.

Michael Caterina and the capsaicin receptor

How the Julius lab found that an ion channel senses heatMakoto Tominaga, Toby Rosen and TRPV1 heat sensation

Nobelists postdoc searches for a receptor for mint and cold

Patapoutians postdoc unearths the powerful Piezo geneBertrand Coste and the pressure receptor

Nobelists lab pins down pressure sensing in miceSeung Hyun Woo, Sanjeev Ranade and Piezo2 in the sense of touch

The rest is here:
Bertrand Coste and the pressure receptor - American Society for Biochemistry and Molecular Biology