Category Archives: Molecular Medicine

BioinformaticsMarket: Introduction

According to the report, the globalbioinformatics marketwas valued at US$24.7Bn in 2020 and is projected to expand at a CAGR of5.9%from 2021 to 2028. Bioinformatics is used to manage the data gathered from research & development projects in the biopharmaceutical, life sciences, and biotechnology industries. Growth of the bioinformatics market is driven by rise in applications of IT in the healthcare sector, along with robust technological advancements. The usage of information technology or IT has enabled easy storage, processing, access, and retrieval of data.

Additionally, the demand for advanced treatment of several diseases and effective preventive solutions is rising. Hence, healthcare professionals focus on research & development projects. Moreover, surge in R&D activities has led to rise in data generation, which increases demand for efficient technology for data management in the healthcare sector.

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Usage of Bioinformatics in High Throughput Screening

The high throughput screening is an emerging bioinformatics field that performs biological tests at high speed with the help of data processing software, sensitive detectors, and liquid handling devices. Increase in importance of high throughput screening in drug discovery is likely to drive the global bioinformatics market over the next few years.

Platforms Segment to Dominate Global Market

The global bioinformatics market has been segmented into services, tools, and platforms. These are commercially available for the purpose of processing the data obtained from various research & development projects employing bioinformatics. In terms of consumption, the platforms segment dominated the global market in 2020, accounting for leading share. The growth of the segment can be attributed to rise in usage of bioinformatics in the process of drug discovery and increase in research & development activities. However, the services segment is projected to dominate the global market during the forecast period.

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Molecular Medicine Segment to Dominate Market

Bioinformatics has applications in preventive medicine, molecular medicine, gene therapy, drug development, and others. Other application areas include forensic analysis of microbes, genetic research for antibiotic resistance, and veterinary science. The molecular medicine segment accounted for the largest market share in 2020. The drug development segment is anticipated to expand at the highest CAGR from 2021 to 2028.

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North America to Dominate Global Market

In terms of region, the global bioinformatics market has been segmented into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. North America dominated the global bioinformatics market in 2020, followed by Europe. Availability of developed technology, structured regulatory framework, higher adoption rate of new technology, and significant investment in research & development by companies boost the growth of the bioinformatics market in North America and Europe. Asia Pacific is a lucrative market for bioinformatics. Factors such as surge in government initiatives to boost biotechnology research & development activities in respective country, increase in funding, rise in awareness about bioinformatics, and surge in literacy rate are expected to fuel the growth of the bioinformatics market in Asia Pacific.

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Competition Landscape

The global bioinformatics market is fragmented in terms of number of players. Key players in the global market include Accelrys, Inc., ID Business Solutions, Ltd., Affymetrix, Inc., CLC bio A/S, Agilent Technologies, Inc., GenoLogics Life Sciences Software, Inc., Life Technologies Corporation, and Illumina, Inc.

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Bioinformatics Market Size will Grow Profitably in the Near Future - Digital Journal

A spring Easter fully fills tourist places and restores confidence after two years of pandemic in Italy, but a study shows that Omicrom and its variants are lethal to the unvaccinated. Italy also has 10% more deaths than the rest of Europe, which maintains a certain concern.

Professor Fabrizio Precliasco, from the University of Milan, pointed out that the data from the study carried out in Hong Kong revealing that Omicron 2 and its variants more related ones are as deadly as the ancestral variants of Covid-19.

Pregliasco said that the illness does not turn into a cold with the advancement of omicron 2, the dominant virus. There is an objective reduction of the worst effects with those who have received the two, three and now fourth doses of Pfizer or Moderna, but the risk of mortality is similar to the times when they began to apply the vaccines, in 2021.

Easter is a test bench, says the expert Pregliasco, who invites citizens to use good senseto gradually recover normality because the virus is still circulating And it does a lot of harm.

In 2020 there were 79 thousand deaths from the pandemic in Italy, which fell to 53 thousand in 2021. Until the first fortnight of April, 22 thousand more deaths are registered.

CASES0.000.000

per million inhab.

DEATHS00.000

Fuente: Johns Hopkins Chart: Flourish | Infographic: Clarion

The government has begun to apply the fourth dose to those over 80 years of age and to frail patients with a series of diseases. Along the way, it is expected to advance to the other age groups. There is no certainty that the youngest should also be vaccinated But this will be indicated by the reality of the infections and the spread of the most serious cases, Pregliasco said.

Health Minister Roberto Speranza said that after May 1 they will adopt the new orientations. The day before expires the obligation to use masks in closed places.

Speranza said that he believes that in schools, students over the age of six should continue to wear a mask in class until the end of the school year.

The North American cardiologist Eric Topol, professor of molecular medicine, confirmed that the Omicron 2 and related variants, already dominate in most of the world. And he highlighted the cases that have occurred in southern China and that led the government to establish the quarantine of the 26 million inhabitants of Shanghai.

People in protective gear walk the streets of Shanghai on Monday. Photo: EFE

With drastic measures of isolation, vaccinations and controls, it had prevented the penetration of the Covid 19 virus. In the first two years of the pandemic in southeastern China, 12,531 cases were registered with 213 deaths. The important wave came this year, guided by Omicron 2.2, which caused more than 1.1 million infected with 7,900 deaths.

Specialist Topol highlights how precious Hong Kongs experience with Omicron 2 is, which attacked a population with a previous low exposure to the virus, In the Italian case, local scientists warn that the greatest risk of a pandemic that is in a recession phase but remains activesuffered by infected patients who they did not complete the vaccination.

They appear to have a mortality risk similar to those who were infected in the ancestral strains of sars-Cov-2.

The famous microbiologist from the University of Padoa Andrea Crisanti, with several daily statements in front of television cameras, has its own theory. In his favor is that he always thinks and is rarely wrong.

With the rate of contagion that Omicron has, containment measures no longer work. In Shanghai they have been in quarantine for a month and the end is not in sight. If you can not contain it is better make it circulate more freely to the virus, strictly protecting the elderly and the frail sick.

Crisanti presents his strategy like this: No masks in closed places and quarantine for the one who is positive. With micron, the priority has changed, which is no longer controlling the spread of the virus but dont make the frail sickbecause if it infects a child under fifteen years of age, nothing happens and, on the other hand, if it happens to an elderly person with other diseases, they can still lose their lives .

The laboratory director virologist at the University of Padua launched his lunge, against giving the anti-Covid vaccine together with the flu. I think that It is a commercial operation because the flu with containment measures has practically disappeared.

On the weekend in Italy the infected and the dead decrease because there are fewer controls. Nevertheless deaths reached 210 and those infected were 115,148 between Saturday and Sunday.

In Italy there are currently 1.22 million infected in their homes. The data of the 9,758 common hospitalized patients are reassuring, with a decrease of 120 compared to Friday and only 403 in intensive care: less than eight in 24 hours. In March 2020, the maximum peak of 4,300 hospitalized in intensive care was reached, the most seriously ill.

Rome, correspondent

ap

TOPICS THAT APPEAR IN THIS NOTE

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Pandemic: why in Italy about 100 people per day still die of covid? - Zyri

A team of scientists, co-led by Luke Hoeppner, Ph.D., assistant professor and leader of the Cancer Biology research section at The Hormel Institute, and Stephen Ekker, Ph.D., Professor of Biochemistry and Molecular Biology at Mayo Clinic and Dean of the Mayo Clinic Graduate School of Biomedical Sciences, recently published findings from preclinical studies that could lead to treatments that reduce inflammation and pathology associated with sunburn.

The article, Vascular Endothelial Growth Factor as an Immediate-Early Activator of Ultraviolet-Induced Skin Injury, was published in Mayo Clinic Proceedings, a premier general medicine journal.

The negative effects of sunburn are relatively common and can range from simple redness to hospital visits and are known to eventually induce inflammation. For example, in the United States, sunburn leads to 30,000 emergency room visits every year.

Repeated sunburns can cause skin cancer.

While current treatments relieve the pain and symptoms, those approaches do not reverse the cumulative effects of sunburn, in part because they only target secondary or tertiary effects of UV exposure. Dr. Hoeppner and his team report on an early molecular cause of sunburn.

We hope that we can target this molecular cause to reduce the negative consequences of sunburn, Hoeppner said. We discovered a new step in the process of sunburn that occurs before inflammation, which opens a new post-exposure window to potentially inhibit all of the negative effects of sunburn. We found that targeting a molecule called vascular endothelial growth factor (VEGF) reduces the subsequent inflammation and pathology associated with skin damage caused by sunburn.

The authors emphasize that future clinical studies would be needed to determine the possible value of VEGF inhibitors as a topical sunburn treatment in humans.

The approach we used in this study was designed to explore options for potential topical treatments, Ekker said. We added VEGF inhibitors after initial UV exposure, to model what happens when people are sunburned and also long after exposure. People often do not realize they are getting sunburned until after they start feeling warm or get flushed. We were able to see VEGF signaling activating in human samples and this strongly suggests there are options to develop interventions and prevent these negative effects.

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Institute and Mayo scientists publish research on preventing associated sunburn effects - Austin Daily Herald - Austin Herald

The new study was published in the journal Nutrients. It was the work of researchers associated with Zhejiang University of Technology in Huzhou, China and an employee of Longevity Valley Botanical Co., Ltd., in Hangzhou, a 113-year-old company devoted to the development of health products based on fungi. The research was funded by public and industry sources.

The researchers used acute gastric injury induced by ethanol in lab rats as a model to test the effects of various polysaccharides derived from Ganoderma lucidum, colloquially known as reishi mushroom.

Reishi is one of the longtime mainstays of Traditional Chinese Medicine (TCM). The 2011 text Herbal Medicine: Bimolecular and Clinical Aspects published by Taylor and Francis has this to say about the fungus:

In Chinese, the name lingzhi (as rendered as reishi) represents a combination of spiritual potency and essence of immortality, and is regarded as the herb of spiritual potency, symbolizing success, well-being, divine power, and longevity. Among cultivated mushrooms, G. lucidum is unique in that its pharmaceutical rather than nutritional value is paramount. A variety of commercial G. lucidum products are available in various forms, such as powders, dietary supplements, and tea. These are produced from different parts of the mushroom, including mycelia, spores, and fruit body. The specific applications and attributed health benefits of lingzhi include control of blood glucose levels, modulation of the immune system, hepatoprotection, bacteriostasis, and more.

An issue with the effects of many TCM preparations from a Western scientific point of view has been that these are multicomponent formulas with many active constituents. That makes parsing out precise modes of action difficult. The same is true for reishi.

To drill down deeper into reishis effects the authors of the present study decided to focus on the polysaccharide fractions of the mushroom. After extracting the polysaccharide fractions of the fruiting body, the researchers used progressively finer filtration membranes of 100 kDa, 10 kDa ad 1 kDa to divide the polysaccharides into three groups by molecular weight that averaged 322.0 kDa, 18.8 kDa, and 6.4 kDa, respectively (kDa=kilodaltons).

The test rats were divided into several groups, with the experiment groups having had gastric injury induced by ethanol administration. Ethanol is what the researchers called an acute gastric mucosal injury model. Ethanol can act directly on the gastric mucosa, leading to erosion, bleeding, perforation, and other injuries.

Direct examination of the texture and integrity of the mucosal walls of the rats guts was one of the primary outcomes of the study. Other outcomes included measurement of antioxidant molecules in the serum, such as superoxide dismutase (SOD) and glutathione peroxidase-1 (GPx-1).

The researchers found that the higher the molecular weight of the polysaccharide, the greater the effect in lessening the gastrointestinal injury caused by ethanol.

GLP100 has a greater improvement effect on acute gastric greater improvement effect on

injury than GLP10, and GLP10 has a better effect than GLP1, the researchers wrote.

There are still many contents that are worth further study. For instance, further separation and purification of GLPs are needed to determine efficacy. For instance, further separation and purification of GLPs are needed to determine efficacy. The synergistic effect of the components of each GLP fraction on gastrointestinal protection, and which proportion of GLP components are more effective when mixed in proportion are worthy of further study, so as to make the research results viable to application, the authors concluded.

Source: Nutrients2022, 14(7), 1476; https://doi.org/10.3390/nu14071476Gastroprotective Effects of Ganoderma lucidum Polysaccharides with Different Molecular Weights on Ethanol-Induced Acute Gastric Injury in RatsAuthors: Tian B, et al.

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Study finds different gastroprotective potential for reishi components based on molecular weight - NutraIngredients-usa.com

Licorice root and black licorice candy. A licorice-derived substance may have anti-inflammatory and anti-cancer effects.

Licorice is more than a candy people either love or hate it may play a role in preventing or treating certain types of cancer, according to researchers at the University of Illinois Chicago.

Gnanasekar Munirathinam and his research team are studying substances derived from the licorice plant Glycyrrhiza glabra to determine if they could be used to prevent or stop the growth of prostate cancer. Munirathinam is an associate professor in the department of biomedical sciences at the College of Medicine Rockford.

A research review into molecular insights of a licorice-derived substance called glycyrrhizin for preventing or treating cancer conducted by Dr. Munirathinam and student researchers suggests further research could lead to specific agents for clinical use.

The journal Pharmacological Research recently published the study titled Oncopreventive and oncotherapeutic potential of licorice triterpenoid compound glycyrrhizin and its derivatives: Molecular insights.

When we look at the research out there and our own data, it appears that glycyrrhizin and its derivative glycyrrhetinic acid have great potential as anti-inflammatory and anti-cancer agents, Munirathinam said. More research is needed into exactly how these could best be used to develop therapies, but this appears to be a promising area of cancer research.

Should everyone go out and eat a bunch of licorice? Probably not, because it may affect blood pressure, interact with certain medications, and cause serious adverse effects, including death, when used excessively. An occasional sweet treat of licorice candy or tea may be better options until more studies can show how to best harness the plants benefits.

Very few clinical trials in humans have been conducted, Munirathinam said. We hope our research on prostate cancer cells advances the science to the point where therapies can be translated to help prevent or even cure prostate and other types of cancer.

Reference: Oncopreventive and oncotherapeutic potential of licorice triterpenoid compound glycyrrhizin and its derivatives: Molecular insights by Rifika Jain, Mohamed Ali Hussein, Shannon Pierce, Chad Martens, Preksha Shahagadkar and Gnanasekar Munirathinam, 19 February 2022, Pharmacological Research.DOI: 10.1016/j.phrs.2022.106138

College of Medicine Rockford students Rifika Jain, Mohamed Ali Hussein, Preksha Shahagadkar, Shannon Pierce and Chad Martens are co-authors of the review, which was partly supported by the National Institutes of Health (R0CA227218) and Brovember Inc.

Originally posted here:
Substance Derived From Licorice May Have Anti-Inflammatory and Anti-Cancer Effects - SciTechDaily

Antibody-drug conjugates (ADCs) illustrate the continued evolution of treatment options across HER2-positive breast cancer, hormone receptor (HR)positive, HER2-negative breast cancer, and triple-negative breast cancer (TNBC). Following the success of fam-trastuzumab deruxtecan-nxki (Enhertu) in the phase 3 DESTINY-Breast03 trial (NCT03529110), other ADCs are likely to enter the treatment fold in the future, according to William J. Gradishar, MD.

What we will likely have in the coming years is a series of ADCs that we can use that will extend the duration of therapy and options for patients, Gradishar said in an interview with OncLive following an Institutional Perspectives in Cancer (IPC) webinar on breast cancer.

In the interview, Gradishar spoke about the expansion of ADCs across subsets of breast cancer, along with emerging treatment options within each space. Gradishar is the Betsy Bramsen professor of Breast Oncology, a professor of medicine (hematology and oncology) at the Feinberg School of Medicine, and chief of Hematology and Oncology in the Department of Medicine at Northwestern Medicine.

Gradishar: In the HER2-positive space, there have been major advances in the past many years. It seems like every year we get new drugs, and thats a great thing for [clinicians] and patients [because] its improving patient outcomes. I focused on the evolving landscape in metastatic HER2-positive breast cancer and the emergence of ADCs. [This includes] not only ado-trastuzumab emtansine [T-DM1; Kadcyla] but also the emergence of trastuzumab deruxtecan, as well as the results from other trials and new drugs that are still in development.

What this is showing us is that we have a series of drugs to try. Even when a patient develops disease progression on one [treatment], theres the probability that not only will we have [another agent] to offer [patients] but we have the high probability that theyll benefit from it.

The DESTINY-Breast03 trial showed that trastuzumab deruxtecan is an excellent drug that can be used after patients progress on a [pertuzumab (Perjeta), trastuzumab (Herceptin), and docetaxel] regimen, so T-DM1 will likely get moved back [in treatment sequencing].

I covered other ADCs that are in development, including the results of the phase 3 TULIP trial [NCT03262935] with vic-trastuzumab duocarmazine, which looked better than alternative options that were used for standard of care.

The other area that I talked about was new TKIs, focusing on the phase 2 HER2CLIMB trial [NCT02614794] with tucatinib [Tukysa]. [I discussed] the results of the overall trial, which showed a superior outcome for patients getting [tucatinib, trastuzumab, and capecitabine (Xeloda)] compared with trastuzumab and capecitabine [with placebo]. [I specifically addressed] the enhanced benefits seen in patients with brain metastases. This is the first trial that focused on that subset of patients, where its shown that including tucatinib had a marked effect on central nervous system [CNS] progression-free survival [PFS] and overall survival [OS] in those patients.

There are anecdotes with other HER2-directed therapies for CNS brain metastases, but [tucatinib] is one of the most compelling stories so far. Trastuzumab deruxtecan is starting to develop some data [in patients with brain metastases], but [data] are clearly the most robust for tucatinib in this setting.

The final thing I talked about was subcutaneous trastuzumab/pertuzumab, which is an option for patients who are getting [intravenous] trastuzumab/pertuzumab. [These 2 treatment administrations] are equally effective [with] no new toxicities. [The subcutaneous administration adds] an element of convenience, both in terms of time in the chair and [length] of infusion. That is a good option for patients.

One [area I discussed] was ADCs, in this case, sacituzumab govitecan-hziy [Trodelvy], which is an ADC that targets TROP2. [Previous] data from the phase 3 ASCENT trial [NCT02574455] demonstrated that sacituzumab govitecan was superior to alternative chemotherapy options. The effect was seen regardless of [low, medium, or high] TROP2 expression. Patients who received sacituzumab govitecan had a better outcome, regardless of whether they harbored a BRCA mutation.

Where we must consider our decision making is in patients who are PD-L1 positive. In patients who are PD-L1 positive, we would consider immunotherapy. There are data showing that pembrolizumab [Keytruda] added to chemotherapy improves overall outcomes for patients with a combined positive score greater than 10. Most [clinicians] would proceed with immunotherapy first for a patient with metastatic TNBC. Until it stops working, [immunotherapy] would continue. However, when it does [stop working], a drug such as sacituzumab govitecan could be considered for lines of therapy beyond immunotherapy.

In patients with early disease, the phase 3 KEYNOTE-522 trial [NCT03036488] demonstrated that neoadjuvant chemotherapy plus pembrolizumab vs chemotherapy alone enhanced not only the pathological complete response rate, but, with long follow-up, event-free survival [EFS]. In the preoperative setting, patients do not need to be PD-L1 positive. Pembrolizumab can be used [regardless of PD-L1 status]. For most patients who fit the criteria for KEYNOTE-522, we would now use a pembrolizumab-based regimen with chemotherapy preoperatively. [Patients with] node-positive tumors bigger than 2 cm are those who we would consider for preoperative therapy.

There are things well have to think about for those patients who have still have residual disease after surgery who get preoperative pembrolizumab. Do you simply give them [adjuvant] pembrolizumab alone, or pembrolizumab with capecitabine? If patients harbor a BRCA mutation, would you add a PARP inhibitor? These are all questions that we dont have clear answers on, but those are expanding options for patients who remain at risk for disease recurrence.

Dr Rao gave us an overview of the role of CDK4/6 inhibitors in the metastatic setting and [shared] emerging data in the adjuvant setting. In the metastatic setting, she covered some of the updates, particularly with ribociclib [Kisqali] and fulvestrant [Faslodex], which clearly demonstrates an OS benefit. All the CDK4/6 inhibitor trials with palbociclib [Ibrance],abemaciclib [Verzenio], or ribociclib, as first- or second-line therapy, all showed an improvement in PFS.

We are starting to see the emergence of an OS benefit, particularly with ribociclib and abemaciclib, and more recently with palbociclib to a smaller degree. There is a consistency in the data. Some might argue that the data with ribociclib are the most compelling, particularly when combined with fulvestrant in the second-line setting, but the general idea is that patients should be getting a CD4/6 inhibitor. Theyre all associated with improvements in outcome, and all have manageable [adverse] effect [AE] profiles.

In the adjuvant setting, weve had data with palbociclib that did not show an advantage to adding it to [treatment for] high-risk patients, either in those with residual disease or as an adjuvant therapy. We still have data that has not reported from the phase 3 NATALEE trial [NCT03701334] with ribociclib.

The one data set that we have positive data from is the phase 3 monarchE trial [NCT03155997] with abemaciclib, which [examined] patients who are at higher risk. They could have had more than 3 positive nodes, or if they had fewer than 4 positive nodes, then they had to have other [high-risk] features, [regarding] tumor size or proliferation, that would have conferred a greater risk of recurrence. What was demonstrated in that trial, with short follow-up, was that there was a clear benefit with abemaciclib. When the trial data were first presented, a minority of patients had gone through the entire duration of abemaciclib therapy of 2 years. Now with longer follow-up, more of the total pool of patients have completed their abemaciclib therapy. The data still favor the use of abemaciclib. Weve started using [abemaciclib with endocrine therapy] in patients who fit the criteria for the monarchE trial. Its been included in the ASCO guidelines and the NCCN guidelines as an option for patients.

Dr Kalinsky, who was the presenter of the phase 3 RxPONDER trial [NCT01272037] when it first was presented, gave an overview of the molecular tools we have to decide prognosis and determine the benefit from chemotherapy. He briefly covered the phase 3 TAILORx trial [NCT00310180], which was conducted in node-negative patients and served as the basis for the RxPONDER trial, which was conducted in higher-risk patients with 1 to 3 positive nodes.

From [RxPONDER], we were able to identify a subset of patients with node-positive disease where we would have almost universally recommended chemotherapy in the past. There is a subset of patients, based not only on their recurrence score but also clinical features and menopausal status, where we can defer chemotherapy and not compromise their overall outcome. Dr Kalinsky discussed the RxPONDER trial and its nuances, particularly as it relates to premenopausal vs postmenopausal women and where we might draw the line on who must get chemotherapy and who would not benefit from it.

That [assay] has been a practice-changing tool that we now employ daily in our practice, just as we did with the TAILORx data for node-negative patients. Dr. Kalinsky put into perspective all the data and nicely reviewed how clinicians would employ this data to make treatment decisions in this setting.

The TAILORx trial is an older data set at this point. Based on that data, we can identify patients at very low risk of recurrence who dont require chemotherapy. [As with] RxPONDER, there are many patients with node-negative disease who would have universally gotten chemotherapy [in the past]. Now, because of long-term data from the TAILORx trial, we can feel comfortable avoiding chemotherapy in a significant fraction of patients who would have likely gotten chemotherapy in the past because it does not compromise their outcomes.

The IPC webinar and discussions by both myself and my colleagues reflect that weve made progress in almost every silo of breast cancer and every strategy we use to reduce risk and to identify patients who can avoid or need specific therapies. [Clinicians] sometimes have to have a longer perspective to understand where we started from, and its one of the benefits of being around for a while. Seeing what we were doing 20 years ago was, by some measure, somewhat crude. We have come a long way in terms of dividing breast cancer into subsets, developing therapies for each subset, using molecular tools to identify patients at risk, and [learning] how we can mitigate their risk.

That is different from the landscape I had when I was training, and I suspect in 20 years, what were doing now will be viewed as crude. Well have something new that makes everything we do today look [antiquated]. Nonetheless, what we heard about in the four talks reflects all the progress that has been made to benefit patients.

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Antibody-Drug Conjugates Are Carving Out Expanded Roles Throughout Breast Cancer - OncLive

Olivia Rissland, DPhil, compares RNA to photocopies of pages of books at a library.

RNA is to DNA what photocopies are to precious books in library stacks: An abridged reproduction with a temporary existence, explains Rissland, a scientist with the University of Colorados RNA Bioscience Initiative.

You can read just a few photocopies, and only for a limited time. Understanding those copies depends on where and when you read them. Even then, you get a just a few clues about whats in the book; you dont get the whole story. Those pages wont easily yield the librarys secrets.

What is really cool about RNA is what happens to those photocopies once they leave the library is different for each photocopy, Rissland says.

Figuring out which photocopy to read and how to interpret what its saying before it disappears is a challenging task at best. It becomes a staggering enterprise when considering the numbers.

There are some 20,000 genes in the human genome. In humans, genes vary from a few hundred DNA base pairs to more than 2 million bases. Messenger RNA the temporary photocopy provides a picture of a piece of the DNA, a snippet of the story.

But ask Rissland about the challenge of studying those photocopies and you discover that its more than a practical question for framing a particular study. Its a philosophy.

I think about what research is, Rissland says. Research exists at the boundary of known and unknown. And so, what were always looking for are mysteries and things that dont make sense. We are trying to understand what it is that were missing, that explains what we see.

Rissland, an assistant professor of biochemistry and molecular genetics, joined the CU School of Medicine in 2017 when the school boosted investment into RNA research, thanks to a gift from The Anschutz Foundation and other supporters. Those funds allowed Dean John Reilly, Jr., MD, to target strategic growth opportunities, which is how the RNA Bioscience Initiative, or RBI, was born.

The goal with these investments is to bring together teams of scientists to work on some of the most challenging questions in human health.

I think were very lucky in the RBI, Rissland says. Its easy for us to foster collaborations. There were five of us who were hired in the same search. Were all close enough in our work that we can have a conversation with points of common interest. But were not so close that therell be competition. For me, that is probably the starting point for all the collaborations. We are bouncing ideas with others in the offices right here and then building out from there.

Risslands lab studies what happens to messenger RNA, or mRNA, after its made. Specifically, she and her lab team are trying to understand how the mechanics of protein production and of mRNA destruction connect with one another. Why do some mRNAs get destroyed quickly and others slowly?

The processes are connected, but how remains a multifaceted mystery and a source of endless fascination for Rissland and the team of scientists in her laboratory. Understanding what happens during that interaction could yield insights into genetic factors causing of human disease.

Although all cells have the same collection of genes, cells differ in which genes are turned on and which are turned off. When that process goes awry, adverse health conditions can result, such as cancer, neurodegeneration, or developmental defects.

One area of inquiry for Risslands lab is the impact of translation elongation speeds on how fast mRNAs are destroyed. Translation occurs when the ribosome in the cell reads the sequence on the mRNA and turns that into a sequence of amino acids, thus building proteins.

You have these machines theyre called ribosomes that are the actual interpreters that go between the different languages and make the protein, Rissland says. The speed at which the ribosome moves matters. A way to think about this is like on a freeway.

You accelerate as you get on the freeway, but your speed can vary once youre on the road. That time span between destinations is elongation. Your speed depends on weather, it depends on traffic, and sometimes you slow down or speed up depending on the conditions. In a cell, a traffic jam is a signal that theres a problem, that theres something a little bit wrong about the RNA, then the cell takes action to deal with that, Rissland says.

There are ample opportunities for traffic jams in a cell because the average cell produces 2 million protein molecules every minute. For a researcher, that means there are ample opportunities to explore.

Thats when you sit down and try to come up with what question to ask, she says. You read the literature and you say, Well, what things are here that dont make sense? What things surprise me? Or what is an implication of something that we know if this is true, then that would imply this is true?

Questions shape the experiments, and the experiments provide answers.

The majority of the time it doesnt work the way you think its going to, Rissland says. You think it could be answer A or it could be answer B. And its always answer C.

Surprise endings are nothing new in literature or life.

Rissland had planned to go to medical school after completing her undergraduate degree in Biology, Mathematics, and Classics (Latin) at Brown University in 2004. She was awarded a Rhodes Scholarship and went to University of Oxford where she earned a DPhil in molecular biology.

The plan actually was to come back to the States and go do my MD, Rissland says. Then Id be an MD, PhD, and drive off into the sunset.

Well, plans change, and the sun also rises. In Risslands case, the light on the horizon was the opportunity to become an independent investigator running a research laboratory.

When I came of age as a scientist was right when we started having all of these methods that allow us to ask questions about RNA and answer them. Five or 10 years earlier, this just wasnt possible, Rissland says. For me it was not only that there were all these questions that I wanted to answer, but we also had these tools to answer them. It was just this huge technological revolution. I mean, its like being a kid in a candy store. How could you say no to that?

The advent of high-throughput sequencing technology has allowed scientists to look widely and deeply into the full spectrum of genetic variations and other factors affecting biological change that were impossibly laborious to study for previous generations of investigators.

Classically, we were able to look at gene A or gene B and we looked at them one by one, she says. What high-throughput sequencing allowed us to do is to not look at things one-by-one, but to look at every single gene at the same time and that gives you just so much more power.

Its the power to think about the themes and larger plot of the story rather than paying attention to one or two characters in a book.

I am most interested in general principles, Rissland says. Specific examples dont provide general insight. They are fine, but theyre not what really get me out of bed in the morning. And to know if something is general you need to be able to look at many things. High throughput sequencing, then, is a really good match for the types of questions I like to ask.

After completing her doctorate, Rissland did postdoctoral work at the Whitehead Institute, an independent biomedical research institute in Cambridge, Mass., and then launched her laboratory at The Hospital for Sick Children, which is affiliated with the University of Toronto, in 2014.

Since starting her career as an independent investigator, her laboratory has trained more than 20 young scientists, nurturing their research, preparing them for their own careers, and encouraging them to ask questions.

I think success looks like someone who has taken real intellectual ownership of their project, who pushes back against my ideas, who tells me that Im wrong. I think when they do that, thats the best part. It means that they have the skills so that they can put those ideas into practice.

Its like reading a book that never ends.

Continue reading here:
Reading a Book That Never Ends - University of Colorado Anschutz Medical Campus

In the age of Big Data and Digital Everything, computers, specialised software, and the Internet have become essential tools in every researchers toolkit to accelerate and assist in their research initiatives. In molecular biology, bioinformatics is the driving force behind the researchers endeavours to continue unravelling the secrets behind the genetic code, together with the forces and factors underlying a living organism.

So what is bioinformatics? Bioinformatics is an interdisciplinary field which typically combines computer science along with statistical analysis to predict, treat and solve biological problems. The origin of bioinformatics dates back to the early 1960s, when Margaret Dayhoff and Robert Ledley published a paper describing a computer program called COMPROTEIN, coded in Fortran on punch cards for the IBM 7090 Mainframes, to aid in protein-structure determination.

Advancements in high-throughput sequencing technology, coupled with reduced costs and turnaround time, has seen an exponential increase in the generation and availability of genomic data. Yet, this was also accompanied by computational and data storage challenges. Aided with the widespread availability of the Internet, bioinformatics has created advanced ways to store, organise, explore, extract, annotate and visualise complex data, while requiring constant updating to standardise new resources to ensure their sustainability and ease of use.

Bioinformatics featured heavily in the COVID-19 pandemic, both in the detection and treatment of different SARS-CoV-2 variants. Lung fluid samples were taken from patients with severe respiratory symptoms. The samples DNA was sequenced, followed by bioinformatics processing that helped to filter out known human and microbial DNA, and to assemble the then unknown SARS-CoV-2 genomic sequence. The whole process took 10 days to complete and the newly assembled sequence was compared to other known sequences and was classified as a coronavirus closely related to a strain found in bats.

The applications of bioinformatics also extend to the identification of disease-causing genetic defects, prognosis and drug discovery, among others. If the disease is genetic in nature, it is first connected to the causative genetic alteration. The next step would be to identify a drug target (usually a protein) which would restore normal cellular function or eliminate the malfunctioning cells. The drug would then have to be filtered from a list of all possibilities based on the drug target.

The importance of bioinformatics in this day and age must be accompanied by skilled bioinformaticians to keep up with this fast-paced field. The Masters in Bioinformatics offered by the Centre for Molecular Medicine and Biobanking at the University of Malta is an interdisciplinary program that combines the application of computer technologies to the handling and analysis of biological data. The course provides the essential knowledge to develop new algorithms and apply the latest technologies in order to process biological data generated from experiments. This program is particularly suited to those with a biology or medical science background seeking to acquire computer programming skills, or vice versa.

Tristan Camilleri, Donald Friggieri, and Matthew Pace are enrolled in the MSc in Bioinformatics programme at the University of Malta.

Sound Bites

The largest-ever genetic study of schizophrenia has identified large numbers of specific genes that could play important roles in the psychiatric disorder. A group of hundreds of researchers across 45 countries analysed DNA from 76,755 people with schizophrenia and 243,649 without it to better understand the genes and biological processes underpinning the condition. The new study found a much larger number of genetic links to schizophrenia than ever before, in 287 different regions of the genome, the human bodys DNA blueprint.

Scientists have published the first complete, gapless sequence of a human genome, two decades after the Human Genome Project produced the first draft human genome sequence. According to researchers, having a complete, gap-free sequence of the roughly three billion bases (or letters) in our DNA is critical for understanding the full spectrum of human genomic variation and for understanding the genetic contributions to certain diseases.

For more soundbites, listen to Radio Mocha every Saturday at 7.30pm on Radju Malta and the following Monday at 9pm on Radju Malta 2 https://www.fb. com/RadioMochaMalta/.

DIDYOU KNOW?

In the early years of the BBC, there was a framed warning near the microphone in the radio studio that read: If you sneeze or rustle papers you will DEAFEN THOUSANDS!!!

Venereal diseases are named after Venus, the Roman

goddess of love. Greeks call them aphrodisiac diseases ( ) after Aphrodite, the Greek goddess of love.

Caesars Palace in Las Vegas was built with such a large car park that it used to host Formula One races.

The first Met Office weather forecast took six weeks to come up with and only predicted the following six hours.

For more trivia, see: http://www.um.edu.mt/think.

Independent journalism costs money. Support Times of Malta for the price of a coffee.

See more here:
Understanding bioinformatics, the key to unlocking our genetic secrets - Times of Malta

Total New Medical Entities by Pharma Company 1999-2018. Modified from "R&D efficiency of leading ... [+] pharmaceutical companies A 20-year analysis"

Last week I published an article on the three academic and industry groups that perform detailed analysis of the pharmaceutical industry, evaluate R&D productivity, and look for best practices. In order to improve, we do need to understand where we are and where we are going. If I am making a claim that I can discover a novel target for a broad disease, design a novel molecule, complete Phase 0 human clinical trial, and go into Phase I in under 30 months - how much impact am I making and how does it compare to the traditional approaches in terms of the probability of getting there, speed and cost? How do you compare to the peers? And are you doing the right thing? To answer these questions we do need to have specialist industry observers, and to set the stage I got to talk to Prof. Alexander Schuhmacher and Prof. Oliver Gassmann of the Competence Network for Life Science Innovation at the Institute of Technology Management at University of St. Gallen about their recent papers covering pharma R&D productivity. What comes next is a more detailed analytical piece that many of the pharmaceutical companies will not exactly like.

During the COVID-19 Pandemic we got to observe how the various pharmaceutical companies utilized their R&D, partnering, and market access capabilities to develop and market vaccines, and drugs. It was very surprising to see the established vaccine and anti-viral drug vendors like GlaxoSmithKline (GSK) fail to deliver either vaccine or a drug, while the other giants with smaller vaccine and antiviral franchises performed spectacularly well.

Top pharmaceutical companies by anti-viral revenue in 2017

For example, Pfizer was not even on the list of Statistas top 10 anti-viral pharmaceutical companies but due to the heroic efforts and actions of their CEO, Dr. Albert Bourla, Pfizer made history in both categories by partnering on BioNTech vaccine and developing PAXLOVID, a small molecule viral 3CL protease inhibitor, where they had a starting point since the original SARS scare. His bold actions quickly propelled Pfizer to the top of the anti-viral Olympus.

But COVID-19 is just one example. Many companies just did not want to pivot from their current R&D programs. When the COVID-19 pandemic just stated many companies with significant capabilities decided not to pivot to or allocate substantial resources to the COVID-19 programs. When it just emerged, many proposals to the board of directors were met with This will be another SARS. You will spend the money but it will go away. I am sure that many companies did not pursue anti-COVID-19 programs for this reason and at some companies, including ours these projects got substantially delayed.

Screenshot of the Amazon.com website for the bestseller by Dr. Albert Bourla, "Moonshot"

From what I hear from the market is that Dr. Bourla let go the strategy advisors that were recommending against going after COVID and mobilized all internal R&D resources to get PAXLOVID on the market setting many industry records and saving millions of lives - a heroic achievement worthy of a Nobel Peace Prize. So we can clearly see that in the face of adversity, the pharmaceutical companies can mobilize and deliver spectacular results. Fortunately, we can read the public side of the story in Dr. Albert Bourlas new book, Moonshot.

As pharmaceutical companies begin to rely on internal data science and AI, how do they decide the amount of expenditure required for efficient use of R&D resources? A comprehensive analysis of the productivity in the pharmaceutical industry will help streamline the industry into cutting waste and developing meaningful new molecular entities (NMEs).

The August 2021 edition of Drug Discovery Today contained an article titled R&D efficiency of leading pharmaceutical companies A 20-year analysis that was written by heavy-hitting academics and industry experts: Alexander Schuhmacher, Oliver Gassmann, and Lucas Wilisch of University of St Gallen, Michael Kuss of PricewaterhouseCoopers, Andreas Kandelbauer of Reutlingen University, and Markus Hinder of Novartis Institute of BioMedical Research.

Screenshot of the article "R&D efficiency of leading pharmaceutical companies - A 20-year analysis" ... [+] in Drug Discovery Today, April 9, 2022

In this study, the group took 20 years-worth of data from 1999 to 2018 comprised of financial, drug output and bibliographic data, to conduct a qualitative and quantitative comparative analysis of 14 leading pharmaceutical companies to identify success factors for R&D efficiency.

NMEs per Year 1999-2018. Modified from "R&D efficiency of leading pharmaceutical companies A ... [+] 20-year analysis"

The group also compared the new molecular entities (NMEs) going through the pipelines of leading companies segmented into one of three ways: through internal R&D, through M&A, and through licensing.

Pfizer came in as a clear leader in total R&D productivity over 20 years followed by MSD (Merck US), and Novartis.

Total New Molecular Entities 1999-2018 by Big Pharma Company. Modified from Schuhmacher and ... [+] Gassmann, "R&D efficiency of leading pharmaceutical companies A 20-year analysis"

Despite delivering the highest total number of drug approvals, most of the NMEs developed and approved by Pfizer came through M&A - 29 in total. Only 8 NMEs came through internal R&D. When it comes to the internally-developed drugs, the clear leader was Novartis with 20 NMEs followed by GSK with 13, and then by a tie between MSD and Bristol Myers Squibb (BMS) with 10 each.

Total NMEs by Big Pharma through Internal R&D 1999-2018. Modified from "R&D efficiency of leading ... [+] pharmaceutical companies A 20-year analysis"

Unsurprisingly, most of the approved NMEs in pharma pipelines come through mergers and acquisitions. For example, in 2009 Pfizer acquired another pharmaceutical giant founded in 1860, Wyeth bringing in a large portfolio of drugs. 2009 was a big year for M&A. Same year, Roche acquired Genentech, which had a celebrated portfolio of NMEs several of which came through Genentechs strong internal biology capabilities. So naturally, the top three leaders in M&A over the past two decades were Pfizer, MSD and Roche.

Total NMEs by Pharma through M&A 1999-2018. Modified from "R&D efficiency of leading pharmaceutical ... [+] companies A 20-year analysis"

Another way to advance internal R&D is through licensing. Many pharmaceutical companies in-license the molecules from biotechnology companies. Recognizing promising assets in early stages also requires strong internal capabilities in business development, chemistry, and biology. Here, we have a tie between GSK and MSD with 7 successfully-developed NMEs each, closely followed by Novartis and Sanofi.

Total NMEs by Pharma through Licensing 1999-2018. Modified from "R&D efficiency of leading ... [+] pharmaceutical companies A 20-year analysis"

One finding of this study that surprised me the most was surprisingly average performance by AstraZeneca. Over the past decade, we saw the many celebrated papers by their R&D leadership explaining the internal R&D best practices. We even attempted to replicate the popular 5R Approach by developing 5R-compatible AI pipelines. However, it scored 7th out of 14 in internally-developed NMEs, 5th in NMEs through M&A, and 11th in licensing.

I also noticed that the recent announcements of AI-partnership achievements are not very impressive either. 2+ years from April 2019 announcement of a target discovery partnership to lead identification in December 2021 that generated a lot of hype in social networks, seems to be closer to industry average using traditional approaches. This does not mean AstraZenecas 5R approach or partnership practices do not work or are overhyped. However, looking at the numbers from the Schuhmacher and Gassmann paper, and the AstraZeneca numbers seem to be surprisingly average as they have a perception of being the most productive. In fact, in my popular 2020 article, which was abundantly shared by AstraZeneca itself, it did look like AstraZeneca held the leading position in AI-powered drug discovery and development.

Furthermore, the study compared the leading pharmaceutical companies by the number of scientific publications during this period and showed the leadership of Pfizer (24,564), followed by GlaxoSmithKline (GSK) and Merck & Co. (22,727 and 15,556 respectively).

Total publications by Big Pharma 1999-2018. Modified from "R&D efficiency of leading pharmaceutical ... [+] companies A 20-year analysis"

In terms of cumulative impact factor (CIF), GlaxoSmithKline topped the chart with 104,047, with Pfizer coming in second place with a CIF of 101,825. Roche came in third place with a CIF of 95,603. But I guess that the average impact factor is a more important metric and here Gilead and Amgen, that have the lower total number of papers, are clearly in the lead.

Average impact factor by big pharma 1999-2018. Modified from "R&D efficiency of leading ... [+] pharmaceutical companies A 20-year analysis"

The analysts found that between 1999 and 2018, the R&D investments of the 14 leading pharmaceutical companies increased from US$49.2 billion in 1999 to US$ 87.1 billion in 2018, and that they launched 270 of the 602 NMEs approved throughout the industry.

The study also revealed that the more a company invested in R&D in the past 20 years, the higher was their output (expressed as approved NMEs or as cumulative impact factor). In brief, this paper proves that higher R&D investments are associated with higher R&D output.

To learn more about the study, I reached out to two members of the group - Alexander and Oliver and asked them about the study and their take on how to build up an R&D ecosystem.

What are some of the key findings that are important in this paper?

Alexander: Really surprising for us is the finding the bigger the company [its R&D organization] was, the higher the R&D output was. This is what we described as economies of scale in pharmaceutical R&D in the paper - if you think about it, it makes sense because pharma R&D can leverage from size (resources, competencies, technologies).

Oliver: Yes, and for those companies whose R&D organization is not big enough to profit from economies of scale, its all about building an R&D ecosystem that can mimic the difference in size. In consequence, for some pharmaceutical companies it is advantageous to pursuit of size with M&A, while other should focus stronger on collaborations and strategic alliances with peers in terms of sharing data, competencies, and technologies in open innovation manner.

In this context, the future threat for pharmaceutical companies is not just within the industry itself, but also coming from outside the pharmaceutical sector. In one of our recent publications we described that large parts of the value creation will be captured by new players (new pharma entrants) all in front the Tech Giants. For example, we recently saw Apple getting a first FDA approved smart healthcare device a disruptive technology coming from the outside (see hereto Clayton Christensen's innovator's dilemma). Google/Verify and other tech companies are also entering the pharma/healthcare market. Already today and even more in the future, value creation will come from data and business models will be more data-driven - the only solution for pharma is: Build partnerships with peers to profit from economies of scale and collaborate with tech companies to leverage from economies of scope.

Would it be true to suggest that the larger you are as a company, the more acquisitive you are too?

Alexander: Neither yes nor no. We see both models in the industry one based on knowledge creation and the other on acquisition. Just to name to examples: Novartis has built a very strong and successful R&D organization that leverages from its internal competencies, while Pfizer was very successful with acquiring R&D portfolios (e.g. Wyeth, Warner Lambert, Pharmacia). So, the important question is, how can you leverage from the resources you have and which R&D models suits best to the resources at hand? There is not a simple answer to this complex question.

Looking at individual companies and how they ranked in the paper, were there any surprises when you put this data together and you compared that to the analyst ratings of those companies and what people perceive?

Alexander: As scientists, we are always surprised about the outcomes of our research. Indeed, it looks like that some companies use their R&D resources more efficient than others or have built R&D models that enable them to perform more efficiently.

As we have used data from 20 years, our results are meaningful. For example, a simple calculation is to take the cumulative R&D expenditures of a pharma company over the 20 years and divide it by the number of drugs it launched in that period. Youll see that top 20 pharma companies have (clearly) different R&D efficiencies.

With respect to ratings and ratings companies; this is not our home turf. We are scientists interested in analyzing and understanding specific settings or type of setting as well as generalizing from it. We do not give any company-specific analysis or even investment recommendations. For example, one of our foci is on R&D efficiency, as it is an industry-specific type of challenge. And we analyze and try to understand this complex field and aim at drawing conclusions that are generalizable for the whole industry.

Do you think that findings in this paper should incentivize people to merge, to acquire, to become even bigger? Because if this statement holds true that the bigger you are, the more efficient you are, it probably kind of postulates the mergers and acquisitions pathway for pretty much any pharma company.

Oliver: In very general terms, yes this paper is a template for M&As. But M&As are not new to the industry. Over the past years, we saw several big M&A transactions and countless acquisitions of small biotechs. What might be new to the industry is the acquisition of tech start-up companies that bring along the highly needed digital competencies for a data-driven R&D. Or it is the thinking in R&D ecosystems that include traditional biotech and pharma players but also new partners from other industries. In consequence, we foresee pharma going away from the more traditional path of open innovation with research collaborations and licensing to a new network-based model that is more agile, more smart and may provide better R&D efficiency.

In consequence, those companies who like to address and build up an R&D ecosystem in a more modern way have to think of what I call a win-win-win formula, which means you need to get a win for the users, for the partners, and for your own company. At the end, it's really a question of to whom do you create value for? Its not only that you have to think the great value for the patient or for your customers and for yourself, but also thinking actually stronger for what could you do to be more attractive for your partners in the ecosystem?

Professor Alexander Schuhmacher

Prof. Dr. Alexander Schuhmacher graduated in biology at the University of Konstanz (Germany), in pharmaceutical medicine at the University of Witten/Herdecke (Germany) and made its PhD in molecular biology at the University of Konstanz; he is also a graduate of the Executive MBA program at the University of St. Gallen (Switzerland). Alexander holds a full professorship in life science management at the Technische Hochschule Ingolstadt (Germany). His research focus is on biopharmaceutical innovation management with a specialization on R&D efficiency, artificial intelligence and open innovation. Prior to that, Alexander worked 9 years as professor at Reutlingen University (Germany) and 14 years in various R&D positions in the pharmaceutical industry.

Professor Oliver Gassmann

Prof. Dr. Oliver Gassmann is a professor for technology and innovation management at the University of St.Gallen, one of Europes leading business schools. He is managing director of the Institute of Technology Management. Until 2002 he worked for Schindler and led its Corporate Research as VP Technology Management. He is co-founder of the BMI-Lab which focusses on business model innovation. His research lead to a revolutionary method of how to design new business models: The Business Model Navigator. Oliver has published over 300 publications and several books on management of innovation. His book The Business Model Navigator by Hanser and Financial Times Publishing has been called as a sensation by the leading German newspaper F.A.Z. and became rapidly a bestseller. He is one of the most cited innovation researchers, the most published author in R&D Management.

Excerpt from:
What Are The Most Productive Pharmaceutical Companies?Pharmaceutical R&D Efficiency Review 1999-2018 - Forbes

Would you like to contribute your creativity to an international team of scientists from various disciplines focusing on basic research in the area of molecular life sciences?

The European Molecular Biology Laboratory (EMBL) invites you to apply for PhD positions in Heidelberg, Barcelona, Grenoble, Hamburg, Hinxton (near Cambridge) and Rome. We welcome candidates with diverse backgrounds, such as in Biology, Chemistry, Physics, Mathematics, Computer Science, Engineering and Molecular Medicine.

EMBL provides PhD students with a starting platform for a successful career in science by fostering early independence and interdisciplinary research. The enriching encounter of different nationalities, the friendly and collaborative atmosphere, and the passion for science is what unites EMBL s diverse staff and provides an ideal setting to forge long-lasting connections and make studying at EMBL a formative experience. Our PhD positions are fully funded and offer broad health care and pension benefits.

Full details on how to submit your online application are available here: https://www.embl.org/about/info/embl-international-phd-programme/applica...

The deadline for submitting the application is 19 April 2022.

Recruited candidates would start their work at EMBL latest by mid of October 2022.

For further information, please visit our web page or contact the EMBL Graduate Office (graduate-office@embl.org).

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Exciting PhD positions at the European Molecular Biology Laboratory (EMBL) job with EUROPEAN MOLECULAR BIOLOGY LABORATORY (EMBL) | 288637 - Times...