Robustness
It took us eight weeks of journal club to get through this paper, “Multivalent interactions make adherens junction–cytoskeletal linkage robust during morphogenesis.” There were many counterintuitive answers that challenged my assumptions in the discussions, which made me appreciate the ability of experiments and observations to overthrow old stories (One example being how force and response relate).
I was attracted to the definition of robustness in biology.
Perhaps most unfounded was my immediate association of the word to how strong a person is to the harshness of life coming their way.
The second association comes from networks. Robustness is how many nodes you can randomly remove without collapsing all other nodes and edges. Often, networks that have more edges between nodes are more robust. Additionally, there are often feedback loops which regulate for the network. In this paper, however, the removal, regulation, node, and edge all have more specific connotations.
The biological network here is made up of a bunch of proteins. These proteins are connected to two other bunches of proteins: (1) the cytoskeleton, which generates force by lengthening then getting pulled on from the other end. (2) the junction, which is a thing that sticks out the membrane and bridges with the junction of another cell, and stick them together. So this network is called the linker between the cytoskeleton and the junction.
You can imagine the drama — when the cytoskeleton makes force that pulls one cell away from the other, the junction needs to counter that force to stay stuck together. This opposition creates a molecular tension. In the linker network, the nodes are proteins and the edges are chemical bonds.
In this context, the “removal” of an edge is when a bond disappears between two proteins. That could happen when the cell is getting stretched and the proteins either reach a breaking point of withstanding the force or they adapt to the new survival scenario for the cell and the tissue group. When tension is exerted on this chain between the cytoskeleton and the junction, the bonds could change: proteins that sense force might go to the gene and tell it to make more protein then tell the proteins to go to the place that needs them most. This is the regulation: when there’s more load, the network recruits more support to withstand.
Additionally, the noise that makes molecules jiggle is still in the background and can sometimes tip the interaction over the subtle difference between staying connected and breaking apart. What happens when they break apart completely is that two cells detach from each other and make a little hole. Sometimes the hole is healable and sometimes not, depending on what the cells are able to do during that time of development and how severe the mistakes have compounded.
The questions that I’m left with:
What is the not-machine alternative metaphor for tension, robustness, function?
Are we convinced that proteins sense and recruit based on tension?
What make cells stack into columns? Adhesion or pulling? (We need data, not just theory, to answer this)
How do gaps form? (It feels emergent)
What is the implication of the fastness of diffusion? (Heat dominates)
How do multiple cells enter and exit a composition where they join into a vertex? (They would need to have asymmetric movement in stage 1 vs stage 2, how do they know when to go where?)
I hope to answer partially through reading the textbook “An Introduction to Systems Biology: Design Principles of Biological Circuits” which is sitting on the shelf above my bench. I also want to talk to people outside the lab and the research environment to see how different people approach these questions which are very much integrated into how people think about life, human life, their sensation and experience, their place in evolution and design.
Productivity System
Today’s title is “[]” because that is the checkbox in Markdown. I have been using checkboxes a lot this past two weeks, finally, in todo lists for the lab and the non-lab research.
Why didn’t I keep a daily todo template before? I think (1) I didn’t have the habit, (2) I didn’t feel the need to seek goals. Before this, I was much more focused on journaling and browsing, which were about reviewing what have been found rather than looking for what to find and optimizing the search.
I started being more vigilant about keeping tasks and data because I had some minor mess-ups on tireder days last month. My mentor suggested that I keep the routine written down somewhere. At the same time it was also priority to get the manager view of the open problem and the systems we are using to get its answers. These two ways guide one in daily work towards a big question.
In the lab, I shifted from a todo list to a calendar. This is because I had been underestimating the length of experiments which made me have to sacrifice some tasks and requeset my teammate to do other tasks. I needed to think about how long each thing takes when I plan the week.
Outside the lab, I shifted from a daily todo to a weekly todo for research on physical-emotional awareness, futures, and other personal questions. This is because I wanted to record some week-long patterns in simple view, such as what time of day was I feeling most energetic vs most worried. I wanted to find some patterns and tweak my schedule.
Compared to two weeks ago, when I had just an inbox and a journal and no todo list, the current system makes me more relaxed: I don’t squeeze my brain to decide what to do next every other minute. With the reminder on what to do the next day, I forget things less and I also encounter less moments where I have to address 5 urgent things at once.
There is no downside at the moment.
Things I want to write about
There are many conversations, readings, makings and thoughts that I want to elaborate on and/or share but haven’t got around to. By making a list I hope to order them and tackle one by one in the upcoming weeks.
David Odde’s Durotaxis
Max Wilson’s droplet design
Dynamicland’s molecular makerspace (benefiting very much from Pablo’s voices)
Oxman’s Aguahoja
Prioritization for the scatter-headed
grants for fieldwork that is having a conversation with, inputting from and contributing to local knowledge people (e.g. ATREE from Fritz); these grant projects’ aim, approach, effectiveness
Figure-making
PDE-making
Octavia Butler’s Parable of the Talents
The Feldenkrais method
Ahupua’a
Sugar and potential
Triangle Cytoskeleton Conference recap
COVID lockdown policy in China 2022
Deep learning in cell biology
Second-order continuity & integrity
Meeting mentors and collaborators
Editing as “salvaging” likes and dislikes from what’s prelabeled “trash”
What if we research for those who need the knowledge
I wish you see the role you already have on me and others
Debugging and farming in the wet lab
What do you do to move a project in science forward when you encounter a challenge?
So many ideas… not enough time… I guess the key is to focus on timely doneness. It’s better to have something done than spend all my time ideating and deciding and not having anything in words / visuals / bubbling and growing in the lab.