One of our members Jonathan Williamson has been very busy raising money for research into a genetic condition that affects his family. The genetic mutation SDH-B means that some family members are susceptible to a rare type of NET Phaeochromocytoma. You can read Jonathan's story here. Be sure to listen out for Jonathan and his daughter on the Kaye Adams BBC Radio Scotland programme next Monday at 10:00 am.
The following is an update on the research project in Jonathan's own words.
I managed to raise £30,000 to get some research started into the SDH-B gene to try to understand it. The research has started in Budapest. If people are interested I will post future updates. The following is an explanation of of the research and progress.
Whenever we eat sugar, it is useless to the cells of our bodies until its energy is released in a controlled explosion. That is called metabolism. It is not so much like a big bang, but a slow fizzle, a multi-part disassembly of the ring of carbons that make up glucose: six carbons, joined to twelve hydrogens and six oxygens that fold neatly into a bent ring shaped like the famous Salvador Dali melted clock.
So in summary, the glucose we eat is like solid rocket fuel for the cell that needs more oxygen to be added to release its internal energy so our cells can do useful work and make us survive. How does this occur?
Like the internal combustion engine has pistons where fuel and oxygen are mixed, so does each cell in our body have micro-pistons. These micro-engines are called mitochondria that are so compressed that a teaspoonful would cover the floor of an average sized room. In short, they are packed batteries of folded internal membranes studded with sugar using enzymes. This is how our cells make energy that we depend on to generate internal work and internal heat. That is called thermodynamics or bioenergetics. A critical part of the cycle is where a four carbon carrier molecule meets two carbons split from sugar. This junction occurs near an enzyme called SDH. S has four carbons and has to be energised so it can productively meet two carbons freshly cleaved from sugar.
SDH is such a complicated enzyme that it can be considered like having a sixteen cylinder engine where four of the cylinders work together (SDH-A through B and C to SDH-D) to ensure smooth running at all applied loads, like an electricity grid matches supply and demand. Should energy use become inefficient because SDH fails, a workaround is needed. In the grid example, alternative power sources may be called on and in the engine example, a reserve electric power motor located on each wheel might compensate for cylinder misfiring. But cells can run for years with misfiring cylinders or poor electricity grid infrastructure. They have built in spare capacity that operates with seamless efficiency.
For the most part, when a defunct cylinder SDH-B enzyme fails due to an inherited mutation in SDH-B, it does not matter much because we have one reserve each for SDH-A to SDH-D. This is like a cell phone that loses signal but the network can compensate by rerouting the mast signals or switching provider. Should the workhorse ‘reserve’ copy of the SDH fail to be made, by chance, say after the DNA of the SDH genes getting exposed to some virus or a drug or radiation or too much toxin, then the cell is in trouble. That process can make a phaeo-tumour occur, but not always. The killing of the workhorse can mean nothing, or can be bad news. It all depends of the environment or grid in which the SDH operates. This is very different in different people.
Oxygen was not always present on earth and early molten earth, billions of years ago, had very little oxygen. As oxygen was formed, it was a toxic gas, more toxic than chlorine gas. So ancient life forms such as bacteria, amoebae and worms developed countermeasures to trap, use and take this gaseous rocket fuel for their own use. They made SDH as one part of their armoury of defensive shields. It turns out that when SDH genes are examined, they have not changed much for millions of years. A man called Brenner in Cambridge realised that worms could be very useful models of diseases because they replicated fast and could have their genes manipulated in the test tube. That idea led to our using worms to try to understand what happens after SDH is mutated by exactly reproducing a human mutation, the one that took the life of Sue Williamson at such a young age, in an attempt to understand the link to phaeo-generation.
We used the money raised to make worms with Sue’s mutation. We did that in the USA. Next the worms were shipped to a world centre for worm biology in Budapest. Because of the favourable exchange rates, we ‘leveraged’ the money by a factor of ten to extend the contracts of dedicated staff co-funded by the Hungarian Government. The work is now underway and the first shipment of money goes to Budapest from its home in Cambridge (at Findacure) so we can start work. We will keep you posted.