A new biobank built from diseased tissue can be used to unravel the disorders and test drugs

An organoid – a three-dimensional cell structure – grown from endometrial cancer tissue of a patient. The different colours indicate the depth of the microscopic scan. | Credit: KU Leuven, Stem Cell and Developmental Biology (recorded by co-author Indra Van Zundert)

Biomedical researchers at KU Leuven have found a new way to study endometrial diseases such as endometriosis and cancer. They were able to grow three-dimensional cell structures from diseased tissue of patients. The biobank can be used to unravel the disorders and test drugs.

Diseases of the endometrium are an important cause of infertility. One example is endometriosis, which is characterised by growth of endometrial-like tissue outside the uterine cavity, resulting in chronic abdominal pain and painful sexual intercourse. Up to half of the patients are subfertile or infertile. Treatment usually requires surgery and permanent hormonal therapy, which is incompatible with pregnancy.

Although endometriosis affects one in ten women worldwide in their fertile years, the illness remains taboo. Public figures like actress Lena Dunham and, recently, fashion designer Alexa Chung, who both suffer from endometriosis, are trying to raise awareness about the disease.

Another important disorder is endometrial cancer, the most common gynecological cancer, with tumours growing in and from the endometrium. We need a better understanding of, and more effective treatments for both diseases. But in order to make progress, researchers have to be able to grow and study the endometrium in the lab.

In 2017, Professor Hugo Vankelecom and his team at the Department of Development and Regeneration at KU Leuven developed ‘organoids’ from a healthy endometrium. These three-dimensional cell structures are grown in a petri dish from tissue fragments and cells of clinical biopsies. The organoids accurately replicate the original endometrial tissue.

With this new study, the team have gone even further, developing organoids from a broad spectrum of endometrial diseases, including endometriosis and endometrial cancer. “The organoids form ‘avatars’, as it were, of the diseased tissue and can also be used to test the effect of drugs and new drug candidates,” senior author Hugo Vankelecom (KU Leuven) explains. “Our study shows that endometrial cancer organoids of different patients are each in a specific way sensitive to chemotherapeutic drugs. Further research will show whether such tests can be of help in the clinical treatment of individual patients. This is an example of what we call personalised medicine.”

“We now have a biobank of organoids from endometrium in healthy and diseased conditions. This can help us discover how an aberrantly functioning endometrium causes infertility and then look for treatments. Our new research model offers the potential to better understand and eventually treat uterine diseases such as endometriosis,” concludes Vankelecom.

Learn more: Endometrial diseases can be imitated in a lab dish, new study shows

 

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Unraveling the genetic disease mechanism behind juvenile idiopathic arthritis could lead to new treatment options

Carine Wouters, Adrian Liston, Erika Van Nieuwenhove, Stephanie Humblet-Baron
via VIB

Identical twin toddlers who presented with severe arthritis helped scientists to identify the first gene mutation that can single-handedly cause a juvenile form of this inflammatory joint disease. By investigating the DNA of individual blood cells of both children and then modelling the genetic defect in a mouse model, the research team led by Adrian Liston (VIB-KU Leuven) was able to unravel the disease mechanism. The findings may help to develop an appropriate treatment as well.

Juvenile idiopathic arthritis is the most common form of all childhood rheumatic diseases. It is defined as arthritis that starts at a young age and persists throughout adulthood, but which does not have a defined cause. Patients present with a highly variable clinical picture, and scientists have long suspected that different combinations of specific genetic susceptibilities and environmental triggers drive the disease.

A single gene mutation

In a new study by researchers at VIB, KU Leuven and UZ Leuven, the cause of juvenile arthritis in a young pair of identical twins was traced back to a single genetic mutation.

“Single-cell sequencing let us track what was going wrong in every cell type in the twin’s blood, creating a link from genetic mutation to disease onset,” explains Dr. Stephanie Humblet-Baron (VIB-KU Leuven), one of the researchers involved in the study. “It was the combination of next generation genetics and immunology approaches that allowed us to find out why these patients were developing arthritis at such a young age.”

Modelling a human disease in mice

Parallel studies in mice confirmed that the gene defect found in the patients’ blood cells indeed led to an enhanced susceptibility to arthritis. Prof. Susan Schlenner (VIB-KU Leuven), first author of the study, stresses the relevance of this approach: “New genetic editing approaches bring mouse research much closer to the patient. We can now rapidly produce new mouse models that reproduce human mutations in mice, allowing us to model the disease of individual patients.”

According to immunology prof. Adrian Liston (VIB-KU Leuven) such insights prove invaluable in biomedical research: “Understanding the cause of the disease unlocks the key to treating the patient.”

From cause to cure

Liston’s team collaborated closely with prof. Carine Wouters (UZ Leuven), who coordinated the clinical aspect of the research: “The identification of a single gene that can cause juvenile idiopathic arthritis is an important milestone. A parallel mouse model with the same genetic mutation is a great tool to dissect the disease mechanism in more detail and to develop more effective targeted therapies for this condition.”

And the young patients? They are relieved to know that scientists found the cause of their symptoms: “We are delighted to know that an explanation has been found for our illness and more so because we are sure it will help other children.”

Thankfully, the youngsters’ arthritis is under good control at th?e moment. Thanks to the new scientific findings, their doctors will be in a much better position to treat any future flare-ups.

Learn more: Identical twins light the way for new genetic cause of arthritis

 

 

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A new approach to help the growing problem of antifungal drug resistance

Patrick Van Dijck and Adam Feyaerts

A research team at the VIB-KU Leuven Center for Microbiology has developed a novel screening method to identify antimicrobial properties of volatile substances. With this assay, they tested the vapour-phase-mediated activity of 175 essential oils (EOs) and 37 EO components. Approximately half of them proved active against the most drug-resistant type of Candida. In a context of fungi showing increasing drug resistance, these findings may be useful in both medical and agricultural applications.

The research project, led by prof. Patrick Van Dijck, is rooted in the growing problem of antifungal drug resistance. Candida cells, for example, are quickly becoming tolerant to fluconazole, the most-used antifungal drug. Next to exploring experimental new techniques, scientists also seek to repurpose existing substances. Plant essential oils (EOs), metabolites obtained by steam distillation or cold citrus peel pressing, may offer interesting opportunities: they are made up of compounds that help protect the plant against microbial or herbivore attacks.

Identifying EOs and their compounds

In the VIB-KU Leuven Center for Microbiology, Adam Feyaerts gathered a collection of 175 different EOs, constituting a collection of over one thousand different small molecules. The aim was to identify biologically active compounds present in these complex mixtures. They therefore developed a new class of assay that allowed to identify new volatile substances with antifungal activities over a distance.

Prof. Patrick Van Dijck (VIB-KU Leuven): “We screened our whole collection of EOs for vapor-phase mediated antifungal activity against two human fungal pathogens, Candida albicans and Candida glabrata. Interestingly, we found that approximately half of the EOs and their compounds had vapour-phase-mediated activity against bothCandida species. Surprisingly, C. glabrata, the most drug-resistant species of the two was on average even more susceptible. In contrast, none of the currently used antifungals showed any vapour-phase-mediated activity.”

Numerous potential applications

This is now the first simple test to look for the vapor-phase-mediated antimicrobial activity of molecules. The same assay could also be used to test other biological activity. And although these findings still have to be confirmed in clinical trials, potential applications are numerous.

Co-author Adam Feyaerts (VIB-KU Leuven): “Our findings are for instance a starting point for the development of molecules that could also be used in vaporizers. After all, volatiles can access otherwise hard to reach areas. Think of possibilities such as maintaining hygiene in hospitals or treat patients with lung infections. There are agricultural options too, such as preventing post-harvest contamination or protecting crops against pests.”

Learn more: Plant-derived volatiles may serve as future antifungals

 

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Purifying air and generating power simply by being exposed to light

via University of Antwerp and KU Leuven

Researchers from the University of Antwerp and KU Leuven have succeeded in developing a process that purifies air and, at the same time, generates power. The device must only be exposed to light in order to function.

“We use a small device with two rooms separated by a membrane,” explains Professor Sammy Verbruggen (UAntwerp/KU Leuven). “Air is purified on one side, while on the other side hydrogen gas is produced from a part of the degradation products. This hydrogen gas can be stored and used later as fuel, as is already being done in some hydrogen buses, for example.”

In this way, the researchers respond to two major social needs: clean air and alternative energy production. The heart of the solution lies at the membrane level, where the researchers use specific nanomaterials. “These catalysts are capable of producing hydrogen gas and breaking down air pollution,” explains Professor Verbruggen. “In the past, these cells were mostly used to extract hydrogen from water. We have now discovered that this is also possible, and even more efficient, with polluted air.”

It seems to be a complex process, but it is not: the device must only be exposed to light. The researchers’ goal is to be able to use sunlight, as the processes underlying the technology are similar to those found in solar panels. The difference here is that electricity is not generated directly, but rather that air is purified while the generated power is stored as hydrogen gas.

“We are currently working on a scale of only a few square centimetres. At a later stage, we would like to scale up our technology to make the process industrially applicable. We are also working on improving our materials so we can use sunlight more efficiently to trigger the reactions. ”

Learn more:Polluted air can generate power

 

 

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Is data safety/security really a myth and will it stay that way?

via knowcache.com

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New hacking technique imperceptibly changes memory virtual servers

For the first time ever a team of Dutch hacking experts, led by cyber security professor Herbert Bos, managed to alter the memory of virtual machines in the cloud without a software bug, using a new attack technique.

With this technique an attacker can crack the keys of secured virtual machines or install malware without it being noticed. It’s a new deduplication-based attack in which data can not only be viewed and leaked, but also modified using a hardware glitch. By doing so the attacker can order the server to install malicious and unwanted software or allow logins by unauthorized persons.

Deduplicationand Rowhammer bug

With the new attack technique Flip Feng Shui (FSS), an attacker rents a virtual machine on the same host as the victim. This can be done by renting many virtual machines until one of them lands next to the victim.  A virtual machine in the cloud is often used to run applications, test new software, or run a website. There are public (for everyone), community (for a select group) and private (for one organization accessible) clouds. The attacker writes a memory page that he knows exists in the victim on the vulnerable memory location and lets it deduplicate. As a result, the identical pages will be merged into one in order to save space (the information is, after all, the same). That page is stored in the same part of the memory of the physical computer. The attacker can now modify the information in the general memory of the computer. This can be done by triggering a hardware bug dubbed Rowhammer, which causes flip bits from 0 to 1 or vice versa, to seek out the vulnerable memory cells and change them.

Cracking OpenSSH

The researchers of the Vrije Universiteit Amsterdam, who worked together with a researcher from the Catholic University of Leuven, describe in their research two attacks on the operating systems Debian and Ubuntu. The first FFS attack gained access to the virtual machines through weakening OpenSSH public keys. The attacker did this by changing the victim’s public key with one bit. In the second attack, the settings of the software management application apt were adjusted by making minor changes to the URL from where apt downloads software. The server could then install malware that presents itself as a software update. The integrity check could be circumvented by making a small change to the public key that verifies the integrity of the apt-get software packages.

Advise NSCS

Debian, Ubuntu, OpenSSH and other companies included in the research were notified before the publication and all have responded. The National Cyber Security Centre (NSCS) of the Dutch government has issued a fact sheet containing information and advice on FFS.

‘Hack-Oscar’

The researchers presented their findings this week during the UNESIX Security Symposium 2016 in the United States. Recently they won the Oscar of hacking: the Pwnie for another attack technique that allows attackers to take over state-of-the-art software (such as the new Edge browser on Microsoft Windows) with all defences up, even if the software has no bugs. Moreover, they can do this from JavaScript in the browser.

Learn more: New hacking technique imperceptibly changes memory virtual servers

 

 

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