Category Archives: Transhuman News

February 13, 2017 by Dr. Maren Berghoff A complex tag for DNA-repair: 3D cartoon showing the linkage of ADP-ribose to the amino acid serine in a protein (turquoise). Credit: Max Planck Institute for Biology of Ageing

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send "repair-proteins" to the damaged parts within the DNA. To do this, an elaborate protein language has evolved. Now scientists from the Max Planck Institute for Biology of Ageing in Cologne have discovered the way a new letter of this alphabet is used in cells. This novel protein modification, called serine ADP-ribosylation, has been overlooked by scientists for decades. This finding reveals how important discoveries may be hidden in scientific "blind spots."

In basic science, one often starts a new research project by trying to reproduce, confirm and build upon what others have shown before. This was exactly what a young team of scientists did, led by Ivan Matic, research group leader at the Max Planck Institute for Biology of Ageing, in collaboration with the group of Ivan Ahel at the University of Oxford. The end result was that the team found a new mechanism, turning some old discoveries upside down.

The research group investigates how the cell determines the fate of specific proteins using tags, so called "post-translational modifications." These are small chemical flags, added to proteins in order to activate them and make them functional. They function as letters of a coding alphabet that the cell can use to determine what to do with a specific protein, for instance sending it off to the cell nucleus to repair damage to our genes. "We were investigating one of the most complex tags, which is known as adenosine diphosphate ribosylation (ADPr). Researchers in the field have thought for many years that this tag is added to particular parts of proteins - the amino acids glutamate, aspartate, arginine and lysine. However, when we looked deeply into the data, we always saw the amino acid serine very close by, which made us very suspicious. After a long time of struggling we could show, that actually the amino acid serine is tagged," explains Matic.

The devil is in the details

For non-scientists this may seem like a small detail. But in the cell "factory" this is an important mechanism. It is like discovering a new letter to an alphabet you thought you knew namely the alphabet the cell uses for sending internal messages. The research team could show that this modification plays a crucial role for repairing DNA damage a process that they can now start to decode. Damage in our DNA can cause mutations that lead to a variety of diseases, such as cancer or neurodegeneration. This damage is inevitable, and repairing it is essential for any organism, including humans. Having discovered this new letter in the cell's alphabet, the research team has now also described its molecular mechanism and shown that its usage is widespread. "We found that this modification is particularly utilized by processes important for genome stability. This research opens up new possibilities to improve and increase the efficiency of the DNA repair machinery," comments Juan Jos Bonfiglio, a researcher in the group of Ivan Matic

The blind spot

But how can it happen that this modification has been overlooked for so many years? Tom Colby, a scientist working in the Matic group tries to explain: "Scientists today are supposed to produce and analyse large amounts of data. That means that you rely on pre-developed tools and apply them to biological systems. But the problem is that these tools are sometimes built on assumptions that can cause blind spots. The most interesting results are sometimes hidden in the blind spots nobody thinks of." Matic adds to this: "I am old-fashioned. I like to step back and look at the original data in detail. Without this we would have overlooked this new modification as people did in the years before."

Explore further: Plant regulatory proteins 'tagged' with sugar

More information: Juan Jos Bonfiglio et al. Serine ADP-Ribosylation Depends on HPF1, Molecular Cell (2017). DOI: 10.1016/j.molcel.2017.01.003

Orsolya Leidecker et al. Serine is a new target residue for endogenous ADP-ribosylation on histones, Nature Chemical Biology (2016). DOI: 10.1038/nchembio.2180

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DNA repaira new letter in the cell alphabet - Phys.Org

Chinese biomed ApolloBio negotiated exclusive rights to develop Inovios lead DNA immunotherapeutic for human papillomavirus (HPV), VGX-3100, within China, Hong Kong, Macao and Taiwan. The collaboration and licence agreement covers development of VGX-3100 for treating and/or preventing pre-cancerous HPV infections and HPV-driven dysplasias, and excludes HPV-driven cancers and all combinations of VGX-3100 with other immunostimulants.

Under terms of the deal ApolloBio will fund all clinical development costs for VGX-3100 within its licensed geographies. Inovio will earn $15 million in up front and near term payments, and could receive another $20 million in regulatory milestones, plus double digit sales royalties.

$12 million of near-term payments will be made to Inovio when FDA lifts the existing VGX-3100 Phase III pre-initiation clinical hold, which has been in place since October 2016. The agency refused to allow the start of the proposed Phase III VGX-3100 trial because it wanted additional data on the shelf-life of disposable parts of the CELLECTRA 5PSP immunotherapy delivery device.

ApolloBio has separately agreed to invest up to $35 million in Inovio, after the clinical hold has been lifted. The firms said that the aggregate investment may be kept below an amount that would make ApolloBio the largest shareholder in Inovio.

The firms claim that there are currently no approved non-surgical treatments for persistent HPV infection or cervical dysplasia. Commenting on the deal with Inovio, Dr. Weiping Yang, ApolloBios CEO, said, We are delighted to begin 2017 with a strategic collaboration with Inovio. VGX-3100 is the worlds first therapeutic vaccine being developed for HPV pre-cancers. This collaboration, license and equity investment marks our determination to introduce late stage innovative new drugs to meet severely unmet medical needs within the Greater China region.

Inovio is exploiting its SynCon DNA plasmid technology and electroporation delivery platform to develop DNA immunotherapeutics against multiple cancers and infectious diseases, including HIV and hepatitis. VGX-3100 is designed to activate functional, antigen-specific CD8 T-cells to clear persistent HPV 16/18 infection, and to reverse the development of precancerous cervical dysplasia.

Read more:
ApolloBio Licenses Inovio's Late-Stage HPV DNA Immunotherapeutic for China - Genetic Engineering & Biotechnology News

The age old adage asserts What doesnt kill you makes you stronger. However, this might not be the case for people who suffer from more viral infections.

A new joint study led by UW assistant professor of anthropology Dan Eisenberg indicates that peoples protective stretches of DNA, which cap the ends of their chromosomes, appear shorter if they experience more infections during infancy.

Understanding humans from evolution

The study is part of human biology research, which aims to understand humans from an evolutionary perspective.

[We are] looking at [what] our roots say as mammals, and primates, Eisenberg said. And how that may influence our biology as it is today.

Eisenberg looks across different places around the world where culture, ecology, and evolution may affect different populations in various ways. In this recent study, he used health data from the Cebu Longitudinal Health and Nutrition Survey, which keeps health records of over 3,000 infants born between 1983-84 in Cebu City in the Philippines.

Detailed health data and feeding habits were collected every two months from these infants up to age 2. Researchers recorded the frequencies of diarrhea in particular, since they most likely indicated infections due to environmental and public health concerns in Cebu City at the time. Researchers kept collecting data over the next 20 years. Of these babies, 1,776 provided their blood samples once again as young adults in 2005.

Eisenberg found that adults with more diarrhea infections as infants showed shorter protective stretches of DNA, which may bring them a higher burden of diseases later in their lives.

Telomeres, the protective stretches of our DNA

Telomeres, which cap the ends of chromosomes, play an important role in cellular aging. They protect genes from damage and improper regulation.

The analogy is that telomeres are like little plastic tips at the ends of our shoelaces, Eisenberg said. When these fray, you shoelaces dont work as well.

The telomeres get a bit shorter each time a cell in our body replicates. Eventually, the cell stops replicating when the telomeres become too short. Thus telomeres in peoples cells become shorter and shorter as they become older, making them more vulnerable to health and environmental issues.

Short telomeres are part of the reason why our bodies do not work well as we get older, Eisenberg said. For example, if you accidentally cut yourself, your skin has to make new cells to heal the wound. When your telomeres are shorter, you are less likely able to regrow skin as quickly.

Similar processes happen everywhere in our bodies while cells are being replaced. Shorter telomeres appear to predict increased sickness and earlier death.

Cells of the immune system, such as white blood cells in the bloodstream, have to replicate and create an army of cells to fight off pathogens. If telomeres in these cells are too short, the immune system may take more effort. On the other hand, overcoming infections also shortens telomeres.

There are good reasons to predict [how] early-life infections might be associated with telomeres in later life, Eisenberg said.

Research findings and further questions

While one could quickly draw the conclusion that more infections in infancy results in shorter telomeres and shorter lives, interpreting current research findings turned out to be more complicated.

This was only an association that we found, but we had to consider whether there could be other reasons why we saw this, Eisenberg said. Part of the ways that longer telomeres help to protect our health is [that] they actually can promote better immune function. So another possible explanation for our findings is that infants born with longer telomeres were better able to fight off the infections.

In the midst of receiving more samples from the Philippines as the study continues, Eisenberg is looking into ways to improve the study.

If you manage to get samples very early in peoples life, maybe right after they were born or within the first few months, you can look to see whether kids with longer telomeres have decreased infections, Eisenberg said. When they do get infections, we can get samples later on to see if their telomeres become shorter. That will be an ideal way to study.

Reach reporter Zezhou Jing at science@dailyuw.com. Twitter: @Zz_Jing

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Research finds association between infancy infection and length of protective DNA stretches - Dailyuw