The Nobel Prize in Physiology or Medicine 2014


The first Nobel Prize of 2014 in Physiology or Medicine is awarded by John O’Keefe and May‐Britt and Edvard I. Moser

for thier discoveries of cells that constitute a positioning system in the brain


From the press release (pdf):

How do we know where we are? How can we find the way from one place to another? And how can we store this information in such a way that we can immediately find the way the next time we trace the same path? This year´s Nobel Laureates have discovered a positioning system, an “inner GPS” in the brain that makes it possible to orient ourselves in space, demonstrating a cellular basis for higher cognitive function.
In 1971, John O´Keefe discovered the first component of this positioning system. He found that a type of nerve cell in an area of the brain called the hippocampus that was always activated when a rat was at a certain place in a room. Other nerve cells were activated when the rat was at other places. O´Keefe concluded that these “place cells” formed a map of the room.
More than three decades later, in 2005, May-Britt and Edvard Moser discovered another key component of the brain’s positioning system. They identified another type of nerve cell, which they called “grid cells”, that generate a coordinate system and allow for precise positioning and pathfinding. Their subsequent research showed how place and grid cells make it possible to determine position and to navigate.
The discoveries of John O´Keefe, May-Britt Moser and Edvard Moser have solved a problem that has occupied philosophers and scientists for centuries – how does the brain create a map of the space surrounding us and how can we navigate our way through a complex environment?

Did you know? Nobel Prize in Medicine


Facts and figures in Nobel Prize in Physiology and Medicine:

201 persons have been awarded the Nobel Prize in Physiology or Medicine between 1901 and 2012.

38 Medicine Prizes have been given to one Laureate only.

10 women have been awarded the Medicine Prize so far.

32 years was the age of the youngest Medicine Laureate ever, Frederick G. Banting, who was awarded the 1923 Medicine Prize for the discovery of insulin.

87 years was the age of the oldest Medicine Laureate ever, Peyton Rous, when he was awarded the Medicine Prize in 1966.

57 is the average age of the Nobel Laureates in Physiology or Medicine the year they were awarded the prize.

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Cell: volume 153, issue 1


The cover:

The kind of food an organism consumes has a broad reaching impact on its development, behavior, and lifespan. In this issue, two papers, MacNeil et al. (pp. 240–252) and Watson et al. (pp. 253–266), explore the effects of diet on these life-history traits in the nematode C. elegans. Combining nutrigenomics and network analyses, they find that different diets affect traits via distinct mechanisms. The response to diet is coupled to metabolic changes, and disruptions of some of these specific metabolic pathways correspond to inborn errors of metabolism in humans. The cover features a “native-art-inspired abstraction” of a worm eating a bacterial diet and illustrates the interconnectedness between diet, nuclear gene regulatory networks, mitochondrial networks, and their effects on life-history traits such as development and brood size.

Cover art by Lesley T. MacNeil.

MacNeil L., Watson E., Arda H. ., Zhu L. & Walhout A.M. (2013). Diet-Induced Developmental Acceleration Independent of TOR and Insulin in C. elegans, Cell, 153 (1) 240-252. DOI:
MacNeil Graphical Abstract

Dietary composition has major effects on physiology. Here, we show that developmental rate, reproduction, and lifespan are altered in C. elegans fed Comamonas DA1877 relative to those fed a standard E. coli OP50 diet. We identify a set of genes that change in expression in response to this diet and use the promoter of one of these (acdh-1) as a dietary sensor. Remarkably, the effects on transcription and development occur even when Comamonas DA1877 is diluted with another diet, suggesting that Comamonas DA1877 generates a signal that is sensed by the nematode. Surprisingly, the developmental effect is independent from TOR and insulin signaling. Rather, Comamonas DA1877 affects cyclic gene expression during molting, likely through the nuclear hormone receptor NHR-23. Altogether, our findings indicate that different bacteria elicit various responses via distinct mechanisms, which has implications for diseases such as obesity and the interactions between the human microbiome and intestinal cells.

Watson E., MacNeil L., Arda H. ., Zhu L. & Walhout A.M. (2013). Integration of Metabolic and Gene Regulatory Networks Modulates the C. elegans Dietary Response, Cell, 153 (1) 253-266. DOI:
Watson MacNeil Graphical Abstract

Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus.

There’s also two free papers:

Cabreiro F., Au C., Leung K.Y., Vergara-Irigaray N., Cochemé H., Noori T., Weinkove D., Schuster E., Greene N.E. & Gems D. & (2013). Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism, Cell, 153 (1) 228-239. DOI:

The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain. Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional and pathogenic effects on its nematode predator/host that impact health and aging. We report that metformin increases lifespan by altering microbial folate and methionine metabolism. Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic. Metformin increases or decreases worm lifespan, depending on E. coli strain metformin sensitivity and glucose concentration. In mammals, the intestinal microbiome influences host metabolism, including development of metabolic disease. Thus, metformin-induced alteration of microbial metabolism could contribute to therapeutic efficacy—and also to its side effects, which include folate deficiency and gastrointestinal upset.

Garraway L. & Lander E. (2013). Lessons from the Cancer Genome, Cell, 153 (1) 17-37. DOI:

Systematic studies of the cancer genome have exploded in recent years. These studies have revealed scores of new cancer genes, including many in processes not previously known to be causal targets in cancer. The genes affect cell signaling, chromatin, and epigenomic regulation; RNA splicing; protein homeostasis; metabolism; and lineage maturation. Still, cancer genomics is in its infancy. Much work remains to complete the mutational catalog in primary tumors and across the natural history of cancer, to connect recurrent genomic alterations to altered pathways and acquired cellular vulnerabilities, and to use this information to guide the development and application of therapies.

Read the complete summary

Facts and things about Nobel Prize 2011 in Medicine


The winners of Nobel Prize 2001 in Medicine or Physiology are:

Bruce Beutler and Jules Hoffman

for they discoveries concerning the activation of innate immunity

and Ralph Steinman

for his discovery of the dendritic cell and its role in adaptive immunity

On the Nobel Prize internet site we can read the key publications of the Nobel:

Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science 1998;282:2085-2088.
Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in drosophila adults. Cell 1996;86:973-983.
Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. J Exp Med 1973;137:1142-1162.
Steinman RM, Witmer MD. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci USA 1978;75:5132-5136.
Schuler G, Steinman RM. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med 1985;161:526-546.