Sense and sensibility

Things derive their being and nature by mutual dependence and are nothing in themselves. Buddhist Philosophy.

  • Sense: To perceive something (using two sugar sensors: Snf3 and Rgt2)
  • Sensibility: Sensitivity, susceptibility to feelings, emotionalism, sentimentalism
  • Hap: Fortune; chance (Hap4, a key protein in respiration)
  • Mishap: Bad luck; an unfortunate accident

Blind my syrupy eyes, Snf3 or Rgt2 to no avail,
for I possess latent sense;
dump me in sugar or alcohol and
not expect change as you aspire,
for I squelch your pride and exhibit my virtues,
and I go on forever.

Remove don’t Hap4, please,
for I become crippled and asphyxiated;
unable to survive to the mounting excess
and become I inebriated;
time would’ve come to squelch my pride and exhibit your virtues,
and I succumb to you, unable to go on forever as before.

Life of a senseless (sugar blind) & asphyxiated (wheezing) micro-organism (baker’s Yeast)

Upon respiration, also called breathing, living things take in oxygen & give out carbon-di-oxide, thereby deriving energy from the food they eat. But yeasts, unlike other living beings, tend to produce a lot of alcohol {ex. Beer}, from glucose (food) upon respiration & this process is known as fermentation. Yeasts are the simplest eukaryotes [Eukaryotes have true compartments in them: like a living room, a bed room, a kitchen, a workroom & so on unlike the prokaryotic (Bacteria’s are prokaryotes) counterparts who don’t have any compartment & are analogous to a dormitory] in the evolutionary tree. Fungi exhibit the next level of complexity & the most complex eukaryotes are the mammals (including the humans).

Many of the signalling proteins in yeasts & humans are highly conserved. If you do strenuous exercise, your muscle produces a lot of lactic acid (it is akin to yeast producing alcohol). Cancer cells primarily derive energy by producing lots of acid. So studying the signalling pathway would benefit the glucose related diseases in humans including diabetes & cancer. Since glucose is the most abundant sugar on earth it makes sense that organisms have developed extensive regulation of its catabolism. There are parallels between the yeast sugar metabolism & the diseased/senescent state of eukaryotic cells. Understanding the glucose metabolism in this simple unicellular living being would help us to learn the molecular mechanisms behind some of the deadly diseases like diabetes caused by obesity.

For yeast to eat glucose (food), it needs to be sensed, just like we see the food with our eyes & our taste buds transmit the quality (sweet/sour/salty) of the food. Once the food is taken in, signals are passed on in a regiment manner (Oh yes, cells too have strict hierarchy): commander proteins, which send orders to the messengers (the soldiers) to carry out specific tasks, like switching on or off of a gene which makes a protein. In the microscopic war ground chemical modifications are employed as weapons. My work involved finding out what happens when there were no sensors or commanders or soldiers & how does it affect the outcome of the cell’s behaviour. My PhD project focused extensively on understanding the glucose (sugar) metabolism in baker’s yeast (used in making breads, cakes) by studying yeasts which are deficient in some of the genes which control the fermentative behaviour. Most living organisms derive energy by burning the food to produce a lot of energy, but the baker’s yeast produces copious amounts of alcohol (wine, beer).

My work together with the existing knowledge shows that yeasts can eat glucose even there are no sensors (eyes). Cellular network go haywire if there are no commanders or soldiers. Scientists exploit this property to make microscopic slaves, which can produce whatever compound of their interest.

The glucose metabolism in yeast has close analogy with the car traffic on the Øresund Bridge (a 15 kilometer bridge connecting Denmark and Sweden) (I am borrowing this analogy from Gunar Liden of Lund). There are two ways to come to Copenhagen in Denmark from Malmø in Sweden: either via the Øresund Bridge or via a ferry from Helsingborg in Sweden to Helsingør in Denmark & then taking the Motorway from Helsingør to Copenhagen. The Øresund Bridge is the quickest, but it costs more, whereas the ferry trip is cheaper, but it takes more time. Yeast cells also take the shortest way to produce energy, until certain threshold glucose traffic. When the flow of cars becomes very high, then some cars are forced to take the ferry route. Similarly when the glucose traffic becomes high, yeast prefers to take the ferry way. It has two advantages. The ferry route produces lot of ethanol which is toxic to other organisms, thereby enabling yeast to thrive without competition. Also it enables yeast to grow very fast as there is much less traffic via the ferry route (people prefer the quicker way & don’t mind paying 250 DKK, which leaves more space for the ferry routers). In my work I have deleted the Øresund way of transport and I find that still some of the cells can take the Ørseund way (maybe by swimming !).

It is all about connectedness. Yeast has 6000 genes and the function of only about 4000 genes is known. If we had accepted the one gene one enzyme hypothesis, we should have been able to model the biological system with quantum accuracy. Alas there was a caveat. To understand some thing we have to have its oppositeness. In genetics it is called mutant. To understand how a gene functions, we have to knock it out and ask the question: what effect does the knockage has on the behaviour. We are trying to connect genes to functions but at the same time opening yet another conundrum which needs to be solved by yet another one and so on. Noted particle physicist David Joseph Bohm (1917-1992) wrote ‘Inseparable quantum connectedness of the whole universe is the fundamental reality, and that relatively independently behaving parts are merely particular and contingent forms within this whole’.

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