On October 3, 2022, the Nobel Assembly at Karolinska Institutet announced the 2022 Nobel Prize in Physiology or Medicine had been awarded to Svante Pääbo, director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. The Assembly cited his “discoveries concerning the genomes of extinct hominins and human evolution”. They mentioned the highlight of his research: the seemingly impossible task, at the time, of sequencing the Neanderthal genome. The discoveries that followed from this sequencing project continue to redefine our understanding of modern human origins.
The award showcases the technological advancements made in the analysis of ancient DNA. However, Pääbo’s research had an inauspicious beginning. In 1985, he published the results of his early work, cloning and sequencing DNA fragments from a 2,400-year-old Egyptian mummy (1). Unfortunately, later analysis revealed that the samples could have been contaminated by the researchers’ own DNA (2).
Earlier this year, I had an opportunity to attend a virtual talk presented by leading climate scientist and communicator Dr. Katharine Hayhoe. She began by asking the audience to send in one word that describes how they feel when thinking about climate change. The responses popped up live in a word cloud on Hayhoe’s shared screen:
Those words also describe how I felt when I realized the conclusion to my seriesof blogs on the 2021 Nobel Prizes would address the topic of climate change.
The tight embrace of welcoming hugs, the cozy warmth of a crackling fireplace, the brisk chill of afternoon walks in snowy woods—these are some of the feelings that, for me, make the winter holidays one of the best times of the year. This season, I’m also choosing to be thankful for the biology that makes these sensations possible.
This year’s Nobel Prize in Physiology and Medicine went to two scientists who discovered the receptors that allow us to sense touch and temperature. Joining other sensory mechanisms recognized by the Nobel committee, these discoveries add to our knowledge of how we interact with the world around us.
Kaelin and Ratcliffe’s labs focused their efforts on the transcription factor HIF (hypoxia-inducible factor). This transcription factor is critical in the cellular adaptation of to changes in oxygen availability.
When oxygen levels are elevated cells contain very little HIF. Ubiquitin is added to the HIF protein via the VHL complex and it is degraded in the proteasome. When oxygen levels are low (hypoxia) the amount of HIF increases.
In 2001 both groups published articles characterizing the interaction between VHL and HIF, and these articles were referenced by the Nobel Prize Organization in their press release about this year’s award. (1,2). Both studies demonstrated that under the normal oxygen conditions hydroxylation of proline residue P564 enabled VHL to recognize and bind to HIF.
The use of cell free expression (i.e., TNT Coupled Transcription/Translation System) by both labs was key in the characterization of the VHL:HIF interaction The labs utilized HIF and VHL 35-S labeled proteins generated via the TNT system under both normal or in a hypoxic work station to:
Determine the affect of ferrous chloride and cobaltous chloride on the interaction
Map the specific region of HIF required for the interaction to occur (556-574)
Determine the effect of HIF point mutations on the interaction
Use synthetic peptides to block the interaction
Conclude that a factor in mammalian cells was necessary for the interaction to occur.
It’s October, and for one week this month scientists around the world will be celebrating the work of their colleagues who have helped push the boundaries of science into territory that we take as “familiar” today. The recipient of the 2010 Nobel Prize in Physiology or Medicine is Robert Edwards, notable for his work on human in vitro fertilization. His work along with his the work of his colleague, gynecologist Patrick Steptoe, who developed the technique of laproscopy, led ultimately to the first successful human in vitro fertilization and ultimately the birth of Louise Brown, the world’s first “test tube baby” in 1978. Read the official press release.
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