Nobel Prizes by Emily Lauterpacht

In the last few days, this year's Nobel Prizes for Chemistry and Physiology or Medicine have both been announced. As they both have biological relevance, I decided to find out more about this year's winners and their discoveries.

Nobel Prize for Chemistry

This year's Nobel Prize for Chemistry is equally shared between 3 scientists: Tomas Lindahl, Paul Modrich and Aziz Sancar. They have been awarded it "for mechanistic studies of DNA repair". Essentially, this means they have mapped at a molecular level and explained how cells repair their DNA, protecting this genetic information. The three scientists worked independently, and their individual findings and discoveries are documented below. 

Tomas Lindahl: Whilst heating RNA, Lindahl saw that the molecule rapidly degraded and started to wonder whether, if RNA was so sensitive, DNA was stable for a lifetime. He estimated that there must be thousands of defects created in the DNA every day, but if this was so, reasoned that humans could not exist as they do. He therefore concluded that something must be repairing the DNA to allow humans to survive. 
As learnt at GCSE, the nitrogenous base cytosine normally pairs with guanine through complementary base pairing in DNA. However cytosine can easily lose an amino acid group, and when this occurs, the base tends to pair with adenine. Lindahl realised that something must be protecting against this, and then in 1974 was able to identify an enzyme in bacteria that removed damaged cytosine from DNA.The process, now known as base excision repair, also occurs in humans, and in 1996, Lindahl recreated the process of human repair in vitro. 

http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/popular-chemistryprize2015.pdf

Aziz Sancar: It has long been known that DNA can be damaged by UV radiation. Aziz Sancar became particularly interested by bacteria, which, when exposed to deadly doses of UV radiation, can recover if illuminated with visible blue light. In 1976, Sancar cloned the gene for the enzyme photolyase, which repairs UV-damaged DNA. However, it became clear that bacteria have a second system for repairing UV damage to their DNA that functioned in the dark, which Sancar's colleagues at Yale had been studying since the mid 60s. He was successful in identifying, isolating and characterising the enzymes that were coded for in 3 UV-sensitive strains of bacteria that carried three different genetic mutations (known as uvrA, uvrB and uvrC). Sancar then continued on to carry out in vitro experiments, showing that these enzymes were able to identify and remove DNA damage by UV. This process became known as nucleotide excision repair, and Sancar proceeded to investigate it in humans, finding that although it was more complex, it was chemically similar. 

http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/popular-chemistryprize2015.pdf

Paul Modrich: During Modrich's postdoc, he began to examine DNA ligase, DNA polymerase and Eco RI, enzymes that affect DNA, but soon came across Dam methylase, which attaches methyl groups to adenine in DNA. He showed that these methyl groups functioned as signposts so that a particular restriction enzyme cut the DNA in the correct location. Working with Matthew Meselson, Modrich proved that these methyl signposts were marking that a DNA strand was not defective, and so did not need repairing. This became known as DNA mismatch repair. From here, Modrich systematically cloned and mapped many enzymes work in the mismatch repair process, and towards the end of the 80s, he was able to recreate the mechanism in vitro. We still don't know how human mismatch repair works, as methylation has a different function in our genome, but thanks to Paul Modrich's work, we are one step closer. 

http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/popular-chemistryprize2015.pdf

Nobel Prize for Physiology or Medicine

The Nobel Prize for Physiology or Medicine also went to three scientists this year.  Half on the prize went to Youyou Tu, "for her discoveries concerning a novel therapy against Malaria", and the other half was equally split between William Campbell and Satoshi Omura, "for their discoveries concerning a novel therapy against infections caused by roundworm parasites". Their research has led to drugs that have treated diseases affecting more than 3.4billion people around the world. 

William Campbell and Satoshi Omura: In 1974, Omura isolated strains of a group of soil bacteria called Streptomyces, that were previously known to have antimicrobial properties. He then sent the organisms to Campbell, who isolated avermectins, a class of compounds that kill parasitic roundworms, from the bacterial cultures. After slightly modifying one of the compounds isolated, the drug Ivermectin was developed, and then released onto the market in 1981. Through killing roundworms, the drug has radically lowered the incidence of River Blindness and Lymphatic Filariasis (Elephantiasis).

From left to right: William Campbell,  Satoshi Omura, Youyou Tu

Youyou Tu: In 1967, China set up a national project, with the aim to discover new therapies against malaria. Tu and her team studied over 2000 traditional herbal remedies from China, in the hope of finding one with antimalarial properties. They discovered that an extract from he wormwood plant Artemisia annua was particularly effective. In 1972, a chemically our compound known as artemisinin was isolated, which was developed into a drug. Artemisinin significantly reduces the mortality rates of patients suffering from Malaria, and it is partly down to the work of Tu that malaria rates are down 75%. 

Emily Lauterpacht