I have always been fascinated by microorganisms and the many strategies they use to subvert the host cells that they parasitize. For me, the most interesting aspect of infection is the interface between the invader and its victim – the ways that bugs take opportunistic advantage of features that cells really can’t live without. My PhD project, for example, dealt with how feline leukemia virus uses sloppy replication to spin out a wide range of mutated envelope proteins, thereby tweaking the way virus particles can dock with the host T-cell membrane or do selective damage that facilitate spread. Of course the host can and does retaliate, shifting the goalposts and forcing the viruses to repeatedly up their game in a process that is often called “cat and mouse evolution”.
I’d moved away from pathogen-host interactions in recent years, my research becoming increasingly abstract and biased towards the host cell side. I’ve been gaining valuable insights into how cells maintain and regulate their dynamic shapes and structures – the ruffles, protrusions and pseudopods that cells elaborate in the process of carrying out their day-to-day existence, coordination of which requires a tight and complex communication system close to the plasma membrane. All of this experience is great ammo for microscopic warfare, whether it be against microbes or cancer. In theory, that is. In practice, I was poking and prodding a highly adapted lab strain of cancer cells in Petri dishes. And in so doing, I was straying further and further away from fighting actual diseases, which was the reason I got into science in the first place. I knew it was time for a change, even if my fellowhsip wasn’t about to expire.
Those of you following my blog know about my long struggle to re-enter academic research after a considerable career break, first in biotech and then in science publishing. You’ll have traveled with me though my ups and downs, shared with me the dawning, and disappointing, realization that staying in research might not be possible – as it ceases to be for so many other mature post-docs who haven’t quite found their place in this cutthroat career fray.
After all of this, I never truly expected a happy ending.
It’s not really an ending, since my starting contract is relatively short in the first instance and will require me to raise funds – never a sure bet in the current climate. But it’s a great stepping-stone, and I’m ridiculously thrilled at the prospect of being in the clinic at last.
From the first of February, I’ll be starting up a basic science lab to work closely with my new colleagues in the Division of Medicine who run a busy clinic dealing with urinary tract infections – in particular chronic ones, that come back again and again despite antibiotic treatment. The science is very new and not yet widely studied. I’m simplifying this quite a bit, but what we know is that bacteria physically invade the bladder epithelia and set up infection within the host cell cytoplasm. In principle this is not an easy achievement, given that the engulfed bacteria start out being enclosed in cell membranes, en route for routine disposal. But then, something goes horribly wrong: the bacteria hijack the communication signals between the membranes and the host cell cytoplasm, persuading the prison wardens to let them free. Once released, the bacteria set up a slow-growing, long-term colony inside the cells, in insidious biofilm masses known (in a wonderfully sci-fi way) as “pods”, and in other quiescent reservoirs deeper within the stratified epithelial layers. Safe within, pods can persist for months, completely protected from antibiotics as well as the person’s immune system. At a later date, following completely unknown cues, the pods reactivate, burst out of the bladder and initiate acute infection all over again. My new colleagues have made a lot of inroads with clinical research projects on patients, but what’s been lacking is the basic science line of investigation. And that’s where I come in.
This is a dream project for me. It’s a fantastic biological problem, and I can now use all of my cell biology expertise against a real-life disease, one which causes a lot of misery and economic liability worldwide. It may be possible to extrapolate anything I learn to other occult intracellular infections. And of course, pathogens are often the best way to shed light on our own cellular processes: viruses, for example, revealed the secrets of cancer genes, so I expect to discover new basic cell biology along the way. Best of all, the mentality of this clinic is to translate any basic findings back into treatment as soon as possible. The translational approach (with a proprietary commercialization angle) also opens up an entirely new avenue of funding streams aimed at getting academia and industry working together, which will hopefully bring in the funds I need to grow the lab.
Looking back, I’m shocked that it’s taken me nine whole years to regain my position as a group leader since being knocked off my perch by an ill-timed biotech bankruptcy. But I don’t regret any of the decisions I made along the way, and I am positive that I will be able to stay in academic research where I belong – with a bit of luck and a prevailing wind.