Reading List July 2020
Published:
A couple research articles and some contemplation on my personal goals.
Fluorescence microscopy is perhaps the most powerful and widely-used experimental approaches in modern biology, but is limited by resolution, both in terms of the size of objects that can be seen, how clearly a preparation can be visualized, and how much of a sample can be clearly visualized. Phenomenal progress has reently been made by Stephan Hell’s group with the development of MINFLUX and related technologies, while there have been advances in tissue clearing methods to reduce light scattered by a sample and thus improve how well, and how much, a sample can be resolved.
When light passes between media of different molecular composition, its speed will change - typically, slowing down. The extent of the change in speed is characterized by a material’s refractive index. Complex materials such as cells and tissues have many components - proteins, lipids, cytosol, etc. - and therefore have multiple refractive indices. The intuitive, but not completely accurate, rule of thumb is that, with higher heterogeneity in refractive index, light scattering increases and resolution decreases.
Tissue clearing methods were developed to address this issue by maximizing the homogeneity in refractive indices of biological samples (reviewed here). These methods typically involve removing the cellular components that we mentioned have different refractive indices such as proteins and lipids, while maintaining the spatial organization of cells/tissues. One disadvantage of these methods is that you wouldn’t be able to do any live imaging on these samples, since you’re removing almost everything in a cell besides, hopefully, whatever fluorescent tag or label you’ve added.
Here, Ogawa et al. report that homogeneity in the refractive index of biological samples can be improved by expressing cephalopod reflectin proteins. Very interesting!
If you’ve done a college biology course, you’ve probably heard of the cell cycle at least once. If not, here’s the tl;dr: cells naturally mature through a sequence of controlled growth and divisions. A cell grows in G1 and G2 phases, then duplicates its genetic material (genome) in the S phase, and finally divides in the M phase by mitosis, giving rise to 2 diploid daughter cells. The cell cycle is of prime interest for cancer researchers because cancer cells grow and divide unchecked, and figuring out how to interfere with these aberrant processes or reinforce proper regulatory mechanisms are some potential approaches in cancer treatment.
Ganier et al. claim that, by inhibiting DNA synthesis during the S phase, cells can still proceed through M phase, albeit with lower efficiency (about 75% enter senescence). So, even without expressing oncogenes or other classic carcinogenic mechanisms, it seems that the default regulatory checkpoint between S and M phases is not particularly sensitive to the proper replication of the genome. From the perspective of trade-offs, this could be because earlier checkpoints are much more heavily enforced, so signs that would indicate aberrant replication would be picked up early on.
I don’t read much of the literature on ion channels besides HCN, but a neighbouring lab focuses a lot on KCNQ (aka Kv7), so I took a glance at this review when I saw it pop up on my feed.
The abstract poses the following: Are KCNQs voltage-gated channels that are also sensitive to ligands or ligand-gated channels that are also sensitive to voltage?
When I read that, I was immediately struck by how unique I thought the question seemed. FYI, KCNQ channels seem to require PIP2 for activation, so they could potentially be seen as primarily PIP2-gated and secondarily voltage-gated, or vice versa.
Of course, these are two sides of a coin (to me, at least). In HCN channels, the canonical ligand, cAMP, is not sufficient for channel opening. Instead, its role is mainly facilitatory. On the other hand, hyperpolarization is necessary for opening, and both voltage- and ligand-gating are allosteric. This seems to suggest that HCN channels evolved from Kv-like channels that gained CNG-like properties, rather than the reverse.
- A personal project to learn public health, epidemiology, and related fields.
We are currently in the midst of the largest epidemics in modern history. I love working with data, and I enjoy reading about science, biotechnology, and even regulatory affairs to some extent. In college, I was quite taken by an introductory epidemiology course, but there were unfortunately no advanced courses offered at my school, so I ended up majoring in biology.
I’ve recently been seriously contemplating my future. As a scientist, I don’t have much confidence in being able to eke out a decent living, much less enjoy the work - either at the bench or elsewhere. I once read somewhere that you should feel comfortable about what you’re doing as long as you believe that it is the best thing you could be doing at the moment.
The above was probably offerd to assuage those doing work in basic science - as long as you’re doing good work, feel free to keep going. However, I’m really not that confident in my scientific ability. There’s lots of people out there who are, or could be, doing much better in my position than I am or would. Consequently, I think I should move on to work on something else.
In particular, I think that the pandemic will generate perhaps the biggest, richest dataset of any health-related phenomenon in modern history. We will need to examine this dataset for not only epidemiological insights, but also analyze its legislatory, economic, political, and sociological aspects to guide future policy decisions. I’d like to start preparing myself with the skillset necessary to support these analyses.
My current plan is to spend about one day a week studying from various textbooks on topics including epidemiology, health economics, and mathematical modelling of infectious disease. I’ve collected several textbooks on other topics as well, such as public policy, health policy, and statistical methods. I’m hoping to cover most of this material by the end of 2020. Wish me luck!