Kinase Function Discovery Furthers Understanding of Cell Division
Researchers at the University of Dundee have discovered a new function within cell division where duplicated DNA is split equally between two identical `daughter’ cells. If this does not occur correctly, then health problems such as cancer can arise.
In the division process, enzymes known as kinases modifyother proteins to switch them on and off by adding a chemical group called a phosphate. The main kinase that controls cell division is Cyclin B-CDK1.
A team led by Dr Adrian Saurin at the University’s School of Medicine, has found an additional function for this kinase that, surprisingly, does not depend on its kinase activity. “We found that Cyclin B has a crucial role in activating a checkpoint that stops division until the cell is ready to divide correctly,” said Dr Saurin. “This is important because otherwise the new daughter cells would have an unequal DNA content, a very common feature of cancer cells.
“What surprised us most is that the main kinase did this without adding a phosphate group onto proteins, so it works in a completely different way. We found instead that Cyclin B works as a scaffold to pull one of the main checkpoint proteins to the right place of the cell at the right time.
“We go on to show that this makes the checkpoint strong, which is an important new part of the puzzle that helps to explain how cells divide correctly. It may also give us some clues in the future about how cancer cells divide incorrectly.
“Cancer cells evolve quickly by dividing with errors. Weakening the checkpoint may be one way they do this. The research has given us ideas for new experiments that could eventually lead to an understanding of cancer, but it is too early to say this is going to open doors for new forms of treatment.”
The research was published in The EMBO Journal.
Dr Adrian Saurin
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€5 million Boost for Coronavirus Drug Search
“This investment enables us to bring Dundee’s expertise in drug discovery to bear on Covid-19 and future strains. This is an insurance policy for the future because we want drugs proven to be effective against coronaviruses ready on the shelf when future outbreaks occur.
“This virus is a highly evolved organism that consists of only 28 proteins. It has become incredibly refined and successful by shedding all non-essential components. Therefore, the virus that causes Covid-19 can only replicate by taking over the machinery of a host cell. In doing so it prevents the host cell from working properly, causing organ damage.
Paul Wyatt
Funding of €5 million to develop antiviral treatments for Covid-19 and future coronaviruses, has enabled scientists at the University of Dundee’s Drug discovery Unit (DDU) to begin work on identifying safe, orally dosed candidate drugs with the potential to tackle acute infections and reduce transmission in the general population.
This significant investment by the COVID-19 Therapeutics Accelerator, initiated by the Bill & Melinda Gates Foundation, Wellcome and Mastercard, will support the three-year Lead Optimization for Coronavirus Infections (LO4CVI) project, which along with a primary focus on Covid-19, will also produce broad- spectrum drugs that work against coronaviruses in general, as the coronavirus family has already given rise to diseases such as MERS and SARS as well as Covid-19.
Professor Paul Wyatt, Head of the DDU, said: “Covid-19 will not be the last coronavirus the world will face and even if it is brought under control, we are still in the early stage of what will be a long-term fight.
“The understanding of the role these and key host proteins play, and the knowledge gathered from studying SARS and other coronaviruses, will provide us with starting points in our quest to identify potential drugs. Antivirals work by inhibiting the development of the disease rather than killing a target pathogen, as antibiotics do.
”We are therefore looking for candidate drugs that can stop Covid-19 from infecting new cells or replicating once it has infected the cell. Because we know there are only a small number of virus and host proteins that are essential for Covid-19 to successfully replicate, we can focus our work to hopefully make rapid progress.”
The Drug Discovery Unit was established in 2006 to translate world-class biology research into novel drug targets and candidate drugs. The group works across multiple disease areas and collaborates with global partners to address unmet medical needs.
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C.Diff Treatment Completes Successful Clinical Trials
Second phase clinical trials of a treatment for Clostridium difficile Infection (CDI), discovered at the University of Strathclyde, have been successfully completed having met its targets of safety, efficacy and dose selection. The study, carried out in the US and Canada by Glasgow-based biopharmaceutical company MGB Biopharma, confirmed that the antibacterial treatment MGB-BP-3, has the potential to become the new gold standard, first-line treatment for CDI.
Other compounds related to MGB-BP-3 are now to be investigated in a project led by Strathclyde for their potential to treat COVID-19. The success of MGB-BP-3 in the clinic is very encouraging for this new study.
CDI is a serious and often life-threatening infection of the large intestine and is the most frequent cause of diarrhoea in hospitals and care homes. In the clinical trials, patients with CDI were given MGB-BP-3 twice daily for 10 days, achieving an initial cure and sustained cure of 100% at the optimum dose.
MGB Biopharma licensed the compounds from Strathclyde in 2010.
Professor Colin Suckling, MGB (Minor Groove Binder) compounds inventor at Strathclyde University said: “The news from MGB Biopharma that a MGB-BP-3, a compound discovered in our chemistry department, successfully cures people of Clostridium difficile infection is exciting and hugely significant, not only for these patients but also for further developments of related compounds from Strathclyde to treat other infectious diseases.
Funding Supports Collaboration on RNA Research
Financed as a European Union Twinning project, Johannes Gutenberg University Mainz (JGU) and Masaryk University, the second-largest university in the Czech Republic, have announced plans for close cooperation with regard to research into ribonucleic acids (RNAs).
The three-year project will kick off in January 2021 and receive €1 million in total provided by the EU. The Institute of Molecular Biology (IMB), located on the JGU campus, the European Molecular Biology Laboratory (EMBL) in Heidelberg, and the University of Edinburgh will also be involved in the program.
The Twinning project is intended to support emergent research institutions within the EU13 states that have joined the European Union since 2004. Eligible institutions are partnered with at least two leading international institutions within the respective field of research. In this case, the Central European Institute of Technology (CEITEC) at Masaryk University will receive support in establishing a leading-edge cluster for RNA research.
“We are very proud to have been selected as a partner,” said Professor Mark Helm of JGU’s Institute of Pharmaceutical and Biomedical Sciences, which is participating in the project. “This
reflects JGU’s sterling reputation in the field of RNA research.”
One core element of the project calls for young researchers from Masaryk University to visit JGU to complete part of their training during or after their doctorate. “The coordinators of the project at the various institutions all know one another because they have been working for decades in the same field,” explained Helm. “Collaboration of this kind fosters a great many ongoing academic and even personal relationships that will prove very fruitful for us all in the long run.” Helm anticipates that the project will not just burnish ties to Masaryk University, but to other participating institutions as well.
RNA uses the genetic information stored in DNA (deoxyribonucleic acid) for the synthesis of proteins and thus plays a central role in the functionality of human cells. In recent years, numerous sub-types of this biomolecule have been discovered. Knowledge about the so-called small RNA is of growing importance for the treatment of a variety of diseases.
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“The Strathclyde Minor Groove Binder (S-MGB) project, from which MGB-BP-3 comes, was devised to tackle a wide range of infectious diseases and we have evidence that other compounds in the series are effective in models of fungal and parasitic diseases for which there are no good treatments currently. We are also starting a project to investigate the potential of S-MBGs to tackle COVID-19 supported by the Chief Scientist Office, Scotland and led by my colleague Dr Fraser Scott.
“MGB Biopharma has done an extraordinary job to develop our compound this far and we look forward to further progress together with our excellent academic colleagues at the University of Glasgow and University of Manchester.”
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