Math Reveals the Secrets of Cells’ Feedback Circuitry

[helvella]

If you understand this article - great! Please explain it to me.

The reasons for posting are that there are some fragments that do make sense. That there is a human story in there. And that if you get anything from it, you see that thyroid and parathyroid are starting to be looked at from the engineering perspective.

It is obvious that diogenes and his associates are very much into modelling thyroid processes and trying to understand what really happens in humans. But much of the rest of endocrinology seems to want to duck out of understanding these basic processes.

If you view the video in the link, you can imagine a similar device created by endocrinologists which crashes into then blue book, then zooms away, and even when the book is still, the device will be going back and forth.

SYNTHETIC BIOLOGY

Math Reveals the Secrets of Cells’ Feedback Circuitry

Maintaining perfect stability through negative feedback is a basic element of electrical circuitry, but it’s been a mystery how cells could do it — until now.

quantamagazine.org/math-rev...

The personal bit:

An electrical engineer by training, Khammash first picked up a textbook on endocrinology at Iowa State University during the fall of 1998. His wife, who had just delivered their first child, had developed a postpartum thyroid disorder, and Khammash wanted to learn more about her illness. The text “could have been a book in control theory without the equations,” he said. “This hormone does this, this interaction increases the rate of that, and it closes the feedback loop, it’s the same story over and over again.”

[diogenes Remembering]

I'm not a mathematician, but reading this, I was struck by the need for activation and anti-activation processes to cut down noise in cellular processes and the need for stability in control, which only two opposing factors can achieve, This is directly parallel to thyroid control, where feedforward and feedback control coexist to produce a tightly controlled situation (re FT3 -through FT4 and TSH). Feedback-only control in this system is too singular and can't control as well and respond quickly to change. Perhaps imagine a seesaw. If holding only one end you can keep the level steady, but it needs one force to do so. With the dual system (i.e. a hand at both ends) its easier to make rapid fine adjustments as one force is put against the other - ie activator v anti-activator.

[helvella in reply to diogenes]

Thank you diogenes.

There is another article on the same site which promotes the concept of stability being vitally important.

I remember biology and physics lessons. In Biology "plants are green because they photosynthesise using light". In Physics "green is the dominant light colour in the spectrum". In my head "so why do plants reflect so much green light?".

Obviously, my brain was incapable of taking that thought to the point of asking why and what that really means!

Why Are Plants Green? To Reduce the Noise in Photosynthesis.

Plants ignore the most energy-rich part of sunlight because stability matters more than efficiency, according to a new model of photosynthesis.

quantamagazine.org/why-are-...

[gabkad in reply to helvella]

Great Stuff. I'll read it later when I'm freshly awake. Thanks.

[jimh111]

I read a bit and got tired. It's too long since I studied mathematics. All I can add is that thyroid hormone control isn't as simple as this article 😄. As well as the HPT axis controlling circulating thyroid hormones we have: -

Three deiodinases regulating local and circulating hormones.

Serum transport proteins that regulate bound and free proportions.

Cellular transport proteins that regulate hormone transport into the cells.

Three active thyroid hormone receptors (in humans) that are differentially expressed throughout the body, and change during development and in response to stimuli.

Receptors can bind as monomers, homodimers and heterodimers (with the retinoid X receptor).

Non-genomic actions of thyroid hormones.

and no doubt some things I've missed or are yet to be discovered.

So, I'll skip the maths. I did enough in my youth. Finally, the maths only applies if the system is working perfectly, there are so many ways it can go wrong, not just a damaged thyroid gland.

[HowCome]

Feedback of the thyroid system always reminded me of “P.I.D. control loops” from my training as a chemical engineer (and my practice, tempering chocolate & cooking caramel in continuous flow machines, as a process engineer).

The NHS base treatment uses a very blunt “change input variable (levothyroxine) until target variable (FT4) reaches required set point”.

And somehow, this does work if you are roughly functioning - I think the body’s complex systems deal with the very blunt T4 replacement approach, if you are not too poorly.

At least - my numbers look ok.

My neuro/psych symptomology and the fact I’m not able to survive in work, possibly tells a different story! But while I’m able to get out of bed, and I am not starving or on the street, my GP’s not interested... just letting the list grow until I break.

And I guess thatjimh111 ‘s list nails this broader problem... levels of The four thyroid hormones from the gland are one thing... and how able the body is to actually use them effectively, at a cellular level, is another thing entirely.

[Hidden]

Sorry. Can’t help at all. I did try but I got a bit bored

The only thing that I can contribute relies on rather a pedantic perception of what a plant actually is. I don’t think a plant is green. Its leaves are green but a plant is usually an entity of leaves and flowers. Flowers can be any colour but even when they’re green, there’s no photosynthesis involved as flowers don’t contain chlorophyll.

😉

[Bob00752]

When I first learnt to drive a car, decades ago, my steering was zig-zaggy. I had to notice that I was going too much to the left and turned the wheel too much to the right and vice versa. By the time I took my test, my steering was much smoother and more accurate. This is an example of a feedback loop. At first my reaction time was too slow and the feedback was too heavy, later reaction time speeded up, possibly becoming a reflex action and only small changes (aka perturbations) were needed - much to the relief of my driving instructor, passengers and other road users. Now I don’t have to consciously do this, it is automatic.

In a similar way, diabetics with a glucose pump driven by a continuous glucose monitor can get small but precise changes in their insulin dosage compared with taking a manual reading every couple of hours and calculating the dose. TSH or other thyroid blood tests are taken once or twice a year. You can see that this is a very rough and ready measure and rather than take multiple doses during the day, we take one dose of T4 and in some cases another dose of T3 daily. No wonder it is so hard for thyroid patients to get their dosage right.

The robot in the video had very fast reaction times and quite fast corrections, a bit like when I started driving. You wouldn’t want any vehicle driver to take 6 months to respond though! So it is “horses for courses”. The mathematical models may be the same but the timescales probably differ….. Hope these feedback loop examples are easy to understand and help you with the concept.