Uncovering the origins of cancer in healthy skin

(Written by Iñigo Martincorena, Cancer Genome Project, Wellcome Trust Sanger Institute Cambridge, UK) 

In the year 2001, the sequence of the human genome was announced as a milestone in science history. This represented a nearly complete map of the common genetic information in all of us. The project had taken over 10 years, the work of thousands of scientists around the globe, and it had cost approximately 3,000 million euros. This huge effort marked the beginning of a genomic revolution in biology.

Although it provided an unprecedented wealth of information, a single reference sequence for all humans contained little information on what makes each of us different or on the basis of genetic diseases. Since then, however, sequencing technologies have evolved dramatically. Nowadays, a person can be sequenced in a few days for less than 1,000 euros, and the cost continues to drop rapidly. This has allowed us to go from a single reference human genome to sequencing many thousands of people, unravelling the basis of many diseases and bringing us much closer to an era of personalised genomics in the clinic.

A field that has benefited enormously from the boom of sequencing technologies is cancer research. Cancer is largely caused by mutations that accumulate in our cells throughout life, which make every tumour unique. Genome sequencing can be used to catalogue the entire list of mutations in a cancer, providing a detailed understanding of the basis of any given tumour. The first genome of a cancer was sequenced in 2009 at the Sanger Institute (Cambridge, United Kingdom), where I work as a postdoctoral researcher. Just 6 years later, over 10,000 cancers have been sequenced throughout the world, providing a detailed catalogue of the genes altered across a wide range of cancer types. And this number is predicted to increase to several hundred thousand in the next few years. This is proving to be an invaluable resource for cancer research and, as we continue to learn how to use this vast information, it will significantly improve cancer diagnosis and therapy.

Who do you love more… mom (species 1) or dad (species 2)?

The latest blockbuster ‘Jurassic World’ brings to our theaters a hybrid dinosaur. In their quest for the most terrifying creature ever, the movie’s ‘scientists’ combine traits of different dinosaur species to create the ultimate predator, which turns out to be big, insatiable… and intelligent. Quite obviously, the movie goes far beyond the state of the art of genetic engineering. That said, hybrids actually can be found everywhere in the real world. And some of them are ‘designed’ by us.

A hybrid is an individual that results from the combination of genomes of different species. Mankind has been raising hybrids from old, by controlled pairings of animals and plants to obtain desired traits in crops and cattle. For example, farmers have long been using mules (the hybrid offspring of a male donkey and a mare) to help laboring the fields, and lots of fruits, cereal crops and garden trees are hybrids selected by us to better suit our needs. Have you ever eaten frog legs? Yes, you’re right! Edible frogs are hybrids too.

Here in the Iberian Peninsula, we also have hybrid frogs. When an Iberian green waterfrog, or  Pérez’s frog (Pelophylax perezi) mates with an individual of other European species (P. ridibundus), a hybrid is formed: Pelophylax klepton grafi.  These three species together compose a hybridogenetic complex. This is because ADN of hybrid frogs contains 50% of each parental species but, amazingly, the eggs or sperm they produce contain exclusively P. ridibundus DNA. They can thus perpetuate a hybrid lineage just by mating with another P. perezi (see figure). If you think about it, they are certainly a mixture of two species but, when they mate, they genetically mimic just one of the parentals, so they perform as a ‘sexual parasite’ for the other parental species. That’s why they are called ‘klepton’ (from Greek, ‘robber’).

Example of the origin and perpetuation of a hybridogenetic lineage of Pelophylax klepton grafi. Matings may involve different sexes of each species than those in the figure. Note that, although adult hybrids are RP (2n chromosomes, half of them are from P. perezi and the other half are from P. ridibundus), they only produce R gametes, thereby discarding the whole P. perezi chromosome dotation in their germinal line. 

When hybrid frogs enter the ecosystem, they may outperform parental species, potentially leading them to extinction. Therefore, understanding the processes of hybridization and delineation of ranges of parental species and contact zones is critical for the conservation of involved species. This is challenging because all these species look extremely alike, and thus morphological identification is very difficult. For this reason, molecular tools are necessary to solve biological questions involving hybridization in water frogs.

A group of researchers from the University of Navarra, the Natural History Museum of Madrid and the Doñana Biological Station (CSIC) are developing sets of molecular tools to answer questions such as: ‘What is the distribution range of P. kl. grafi? Did this hybrid klepton originate naturally or as a result of human introductions? Can hybrids mate themselves and produce P. ridibundus offspring? Is the klepton displacing native P. perezi? These genetic markers have proven useful to distinguish among the three species within the complex and, by using them, we can assess the genetic variability of individuals to trace the history of hybrid lineages and solve these and other key issues.

So don’t panic in the theater. If a mad hybrid threatens you, we’ll be ready for it… as long as it is a frog!

Gregorio Sánchez-Montes

PhD Student

Department of Environmental Biology, University of Navarra

The Nano world…can you see it?

New revolutionary airplanes are made of nanocomposites, new cancer treatments use nanocarriers, new hydration creams use nanocapsules to keep you hydrated 24h and nanofibers are changing the clothes we wear. Furthermore, in the food industry nanoparticles in the packaging protect the contents longer from bacteria and degradation. Making planes lighter and stronger, drugs more target-specific, food with less preservatives, new generation cosmetics and smart packaging have one thing in common that is changing our lives: Nanotechnology.

[1] Serra‐Gómez R, Gonzalez-Gaitano G, González-Benito J. Composites based on EVA and barium titanate submicrometric particles: Preparation by high‐energy ball milling and characterization. Polym Compos 2012;33:1549–56.

Cannabinoids: a new frontier for the treatment of Parkinson´s disease

The first evidences about the use of cannabis arise from the second millennium BC, when Assyrians used cannabis or, as they called it, “the drug that takes away the mind” for its psychoactive, mind-altering effects and for its medical properties. Since it was brought to the western world in the 18^th century, its use has been a source of controversy. Surprisingly, research on cannabis has advanced slowly. The major reason was the lack of knowledge about its basic chemistry. Unlike morphine and cocaine, which were isolated and used for research since the 19^th century,  the chemical structures of the psychoactive constituents of cannabis were not isolated until the 1960s. There are over 400 chemicals in cannabis, 80 of them unique to this plant. The exact chemical composition differs between plant species, the parts of the plant and growing conditions. Once the chemistry of the plant was elucidated and the psychoactive molecules identified, it was possible to find the bases of the endocannabinoid system, which is particularly relevant to functions associated with the central nervous system such as pain, mood or apetite. The elements of the endocannabinoid system are highly expressed in brain structures related to movement control, suggesting that they could also be involved in movement disorders such as Parkinson’s disease.