First PhD Checkpoint

In December, we – the (mostly) young and innocent first-year PhD students at the Francis Crick Institute – gave our first formal talks. Each student had to present the outline of their project to all the other students in a ten minute slot. This was probably intended mostly for our own benefit to ensure that we had at least a rough idea of what we will be working on for the foreseeable future. Here I’d just like to mention a few of the talks that I found particularly interesting, but it’s worth saying that I thought the overall level of presentations was very high and the questions we ended up asking each other were well thought through. Overall a very enjoyable experience.

  1. To begin with there were a couple of talks from students in the same lab studying the interactions of cancerous cells with the immune system. In particular, they are trying to find out how dendritic cells – cells that normally alert effector cells of the immune system that something is wrong (e.g. an infection is happening) – can sense the presence of dead/dying tumour cells and relay this information to so-called T cells. The two students are looking at both the molecular mechanism by which this happens, but also whether precursors of dendritic cells in the bone marrow have similar abilities.

  2. A few students in the programme are working on mathematical/computational projects and will never have to wear a lab coat. For example, one lab is interested in understanding how non-cancerous cells near a tumour interact with the cancer cells and influence their ability to move. To do this one can mathematically model the movement patterns of the “cancer-associated fibroblasts” and how they interact with extracellular proteins to form tracks for the cancer cells to move along. In the simplest terms (and that’s the only level at which I understand this), the model relies on the Morse potential, which is normally used to understand how atoms interact but can be scaled up to model interacting cells. Here is a video of a fibroblast interacting with a breast cancer cell; the accompanying text is maybe overly simplistic, but you get the gist:

    Another student is studying how sheets of cells move together, both during embryonic development and tumour formation. This relies (roughly) on modelling cells as polygonal shapes that stick together via their vertices. Yet another “dry” project is investigating how cancers evolve over their lifetime: this is done by collecting DNA sequencing data from cancer cells at various stages of their development and inferring which changes happened when.

  3. Since it is generally the metastases that are the deadly part of cancers it is important to  understand how cells move. There is, of course, a lot of information about this already but here the aim is to find out more about how different cancer cells (e.g. breast cancer and skin cancer) share certain features in their movement patterns.

  4. Not all labs in the institute study cancer. Some labs focus on basic research using yeast as a model organism. Both yeast cells and our cells contain a lot of DNA that is not translated into protein; for a long time all this DNA was termed “junk” and nobody bothered with it too much. It is becoming increasingly clear that this so-called non-coding DNA can still play various roles in the cell and some of these may be deleterious. Therefore one student is studying how cells prevent the activation (transcription) of some of these stretches of DNA.

  5. Another major branch of the institute deals with infectious diseases and the immune system more broadly. Two talks that I enjoyed on this front were given by students again working in the same lab. They are studying “neutrophil extracellular traps” (NETs), which I had never heard of before and sound quite cool. Neutrophils are a cell type of the immune system and are the first to react to infectious agents. By releasing very broad-acting antimicrobials they try to quell an infection in its infancy, but by doing so they also cause the four main symptoms of inflammation: pain, heat, redness and swelling. NETs are made of DNA and proteins from the neutrophils and are sticky. One of the students is looking into how NETs can exacerbate atherosclerosis, while the other is finding out how NETs physically trap invaders, such as the fungus Candida albicans.

  6. Lastly, and because it would pain me not to mention CRISPR, one student is trying to find a way to control the sex ratio of offspring in laboratory animals, specifically mice. While at first glance this might seem dangerous or cruel, it is actually part of an effort to reduce, replace and refine the use of animals in research. For example, if you are studying prostate cancer or ovarian cancer half of the experimental animals born are completely useless and end up being “wasted”. At the moment, some agriculture relies on physically sorting sperm cells into those carrying X or Y chromosomes and using mainly those with X chromosomes for in vitro fertilisation (because far fewer male animals are needed). Although this is a very accurate method it is expensive and time-consuming. Since CRISPR is precise and can be genetically encoded it would virtually work by itself once established.

This is by no means an exhaustive list of the topics covered by our projects, but hopefully it’s an interesting glimpse into what we are currently spending (almost all?) of our brains and energy trying to figure out.

These talks will be complemented with a so-called thesis committee meeting later this month: here each student will present a very similar talk to three professors or group leaders, who will be advising the project from an outside perspective. Hopefully being locked in with three clever and knowledgeable people will conjure up constructive criticism as well as (even more) new ideas!

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