My journey through applied physics and structural biology starting with the ARDD2024

This year I was attending the ARDD only online. It was really great to see, how far the field has come and, whether we need to accelerate it further and if there are more opportunities in the future to lend more time for research and longevity, like IL-11. Then there was also the very much anticipated talk by David Sinclair (and other epigenetic reprogramming researchers). In his talk he mentioned there would be a need for an epigenetic backup copy to restore the young state of the epigenome, but unfortunately he could not find it yet. But here I made the connection:

A few weeks ago I was taking part in a guided tour through the European XFEL in Hamburg, which is in my neighbourhood. One of this marketing ideas is that they one day could make videos of biomolecules’ motions. Basically the facility consists of a linear particle accelerator for electrons and a part, where the electrons energy is converted into high-energy photons, so to have ultra-short pulsed X-ray beams, which can (compared to other methods) deeply penetrate all kind of probes. The signal scattered from those probes is then detected by a x-ray detector and gives a so-called diffraction image. With some computer processing this data is converted into an 3D image of the probe. For example, some of the Covid proteins were imaged in a crystallised form. Also cells, viruses and proteins can be studied there on a close-to atomic scale, so in general very small things.

My idea was then to use those advanced imaging technology to find the epigenetic backup copy. This simple preconception could not withstand further reading, because there were challenging views, like how intrinsically by the cell this information could generated (Anja Groth). But at least it was interesting enough to explore this advanced technology maybe for further investigating the epigenetic processes.

My curiosity lead me then to ask physicists from this research facility, whether it should be possible to image sub-cellular processes, and there I met (online) a detector physicist, who was willing to give me an introduction (last Thursday). So now I needed more input from aging biologists to get to know their needs. In the end two were more interested, and with one I had a short conversation (which was more neuroscience related and needed big MRI machines to more closely resolved investigate the brain, so that was not a match). The other biologist is a group leader specialising in epigenetics at the university hospital in Berlin (Charité). He was really interested in make use-cases for this imaging technology, but wanted to have more technical details about this technology. Then in my conversation with the physicist he himself was working on different scales of resolution, like 1 micro-meter, whereas the chromatin fibre (epigenetics) has a width of 10 nano-meters, but he gave me some contacts of other departments. Before I go ahead talking to more people I really wanted to dig deep in the world or molecular epigenetics.

But this exploration opened my view to for me new fields of biophysics and structural biology and has aroused my interest in different microscopy methods like cryo-electron microscopy (which is more common in biology and many others) and simulations of molecular dynamics (MD). I think with more advanced tools we can better understand the cell biology and in this way help solving aging.

Next week I will have at least one discussion about what I was doing here, so I am looking forward to getting more feedback on this. Also I tried to get direct collaborators, but this was also very hard. But I will attend Zelar city in Berlin for a weekend this autumn and maybe can find more people interested in that approach at least as a general researcher.

One interesting link for a more broader view (“Fostering discoveries in the era of exascale computing: How the next generation of supercomputers empowers computational and experimental biophysics alike“):

https://www.cell.com/biophysj/fulltext/S0006-3495(23)00091-7

“Finding the chink in corona’s armour”

Nucleosome Dynamics Derived at the Single-Molecule Level Bridges Its Structures and Functions

There are also many details involved in the operations of such imaging experiments that might be interesting for a follow-up post.