Elephants : Large Body Size, Peto′s Paradox & tumor suppressor genes.

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Abstract

A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as “Peto′s Paradox“. Here we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes in the elephant (Proboscidean) lineage.

     Furthermore we show that several of the TP53 retrogenes are transcribed and translated and contribute to an enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis via a hyperactive TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto′s paradox in Proboscideans.

Original Article :  bioRxiv

TP53 copy number expansion correlates with the evolution of increased body size and an enhanced DNA damage response in elephants.

Unexpected connections: Calcium refill mechanisms in nerve cells affects gene expression.

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Anusha Krishnan, NCBS

        Calcium, is not just for strong bones – it is an essential requirement for normal muscle and nerve cell function. Recent research now shows that Calcium ion homeostasis in nerve cells is linked to another important process – it may be regulating the levels of an important signalling molecule called dopamine.

Gaiti Hasan’s lab at the National Centre for Biological Sciences (NCBS, Bangalore) has provided fresh insights into how the Calcium molecule is necessary for the myriad mechanisms supporting life. Hasan’s group now show that a process called SOCE (Store Operated Calcium Entry) which works to maintain calcium levels in cells could also play a role in maintaining the levels of the vital neurotransmitter dopamine.

SOCE is a process by which Calcium ions slowly enter nerve cells to refill stores that have been depleted by various activities. Central to this process is a protein named Orai, which acts as a channel that allows the entry of Calcium ions into cells. The ORAI1 gene is known to be important for T-lymphocytes, as loss of this gene function leads to Severe Combined Immunodeficiency syndrome (SCID) in humans.

In Drosophila flies, the Orai gene function is required in neurons for the ability to initiate and maintain flight. The current study used Drosophila flies with mutated Orai genes which did not allow normal SOCE to operate. The Hasan group observed that if SOCE was inhibited during pupal development in certain neurons, the adult mutant flies could not fly. So, Calcium appears to be vital to the wiring process that creates a ‘flight circuit’ in the fly brain. Now why should this be important?

This result is important because it reveals a potential link between SOCE and the neurotransmitter called dopamine. Dopamine is an indispensable neurotransmitter in the brain, controlling motor function, cognitive control and much more. In the flightless Orai mutant flies, SOCE was inhibited in a set of nerve cells called ‘dopaminergic interneurons’ – neurons that used dopamine to relay signals. Further investigations into this phenomenon revealed that SOCE and its role in maintaining Calcium homeostasis in nerve cells affected the transcription of several genes related to dopamine synthesis and transport.

Trayambak Pathak, who has been working with Hasan’s group on Drosophila Orai for his Ph.D, is the first author of the paper describing these results in the Journal of Neuroscience. “We expected that inhibition of the calcium refilling process, ie, SOCE, in nerve cells would impair and ultimately stop their functioning, perhaps by killing them. It was quite a surprise when we discovered instead that it [Calcium homeostasis] was actually affecting neurotransmitter levels. Furthermore – this phenomenon [altered dopamine levels] was effected via genetic regulation, ie, transcription,of dopamine synthesis enzymes and other proteins”, says Pathak.

The implications of this work are intriguing. Inhibition of SOCE in Drosophila seems to specifically affect dopaminergic neurons. The roles of SOCE in mammalian cells are not clear, however, these functions in the dopaminergic neurons might be conserved. If so, it might have some role to play in diseases such as Parkinson’s, Attention Deficit Syndromes (ADS) and schizophrenia. “There is a still so much more to understand in these processes. Our work has opened up a plethora of questions about the importance of SOCE in nerve cells. It may even provide us with new pathways to explore for treatments of conditions such as Parkinson’s disease”, says Hasan.

The study, titled “Store-Operated Calcium Entry through Orai is required for transcriptional maturation of the flight circuit in Drosophila” was published in the Journal of Neuroscience and can be accessed here.

Original News : NCBS News

 

IISER Pune, IIT-Delhi teams wins Bronze Medal at iGEM 2015 contest in Boston; Congratulations

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IISER Pune iGEM 2015 team-members

A team of undergraduates from IISER Pune has bagged a Bronze Medal at the international Genetically Engineered Machines (iGEM) contest held at Boston, USA from September 24-28, 2015.

iGEM first started in 2003 as an Independent Activity Period (IAP) project of undergraduates at the Massachusetts Institute of Technology (MIT) in Boston. It has since grown and gone international with over 280 teams from all over the world participating in 2015. In this Synthetic Biology contest participants are expected to design molecular “bio-devices” in a manner that combines their understanding of genetically encoded parts with additions from anything ranging from art to nano-fabrication.

This year, a team of ten 2nd year BS-MS students from IISER Pune: Siddhesh Zadey, Prachiti Moghe, Rahul Biradar, Gayatri Mundhe, Prashant Uniyal, Ira Phadke, Snehal Kadam, Harsh Gakhare, Swapnil Bodkhe and Yash Jawale signed up under the guidance of Dr Chaitanya Athale (Assistant Professor, IISER Pune). To help them troubleshoot the experimental and theoretical aspects, two PhD students, from the Athale-Lab, Neha Khetan and Manasi Gangan, volunteered to help out. After a hectic summer and last minute experiments, two novel DNA sequences were submitted to the common repository of iGEM. Finally, six of the members were selected to present their work as a talk and poster to the international audience at the Giant Jamboree in Boston, USA.

The IISER Pune team was amongst a list of Bronze-Medal winners – one of only two from India. Their project “Mycobacterium Revelio” was targeted to develop a cost-effective diagnostic tool for detecting the causative pathogen for tuberculosis (TB). Using ideas from synthetic biology, simulations of genetic networks and combined with basic microbiology, the team designed a genetic device they refer to as “the Terminator”. This sequence in its eventual function aims to cause a cessation of cell division when turned on, to keep the Mycobacterial population at a fixed size. Additional modules, “Detection” for instance aimed to use visible dyes that genetically trigger the appearance of colour in the target organism, M. tuberculosis.

This year the IISER Pune team had also hosted a national meet-up of Indian teams participating in iGEM 2015, with groups from IIT Kharagpur and IIT Delhi visiting the institute. The work was funded by IISER Pune, the Department of Biotechnology and corporate sponsorship from Qiagen, Eppendorf and Merck-Millipore, with additional support from Mathworks and IDT.

We congratulate team Mycobacterium Revelio and wish them success in their future endeavours.

Original news : IISER,Pune News.

All iGEM 2015 Results : Click Here

THE NOBEL PRIZE IN PHYSICS 2015 : Neutrinos, the chameleons of space

We live in a world of neutrinos. Thousands of billions of neutrinos are flowing through your body every second. You cannot see them and you do not feel them. Neutrinos rush through space almost at the speed of light and hardly ever interact with matter. Where do they come from?

 

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