When nothing changes everything

It was a quiet afternoon last week when I once again sat down with my best friend the microscope to look at some new samples. I’m currently trying to understand how a certain type of bacterium tricks our macrophages into believing it’s not really there. Macrophages are immune cells, the janitors or the body. They travel from the bone marrow to the tissues to clean up everything from dead cells to dangerous invaders. Some of these invaders are disease-causing bacteria that are able to evade detection and killing by our macrophages. I want to know how they do it.

For this specific experiment I was using macrophages with a GFP-tag attached to the protein I was interested in. This allows me to use a microscope to see if the protein in question is able to find the bacteria. If the protein appears close to or around the bugs it is a very strong indication that they are being sent down a specific pathway.

I was extremely excited about this. Over the last year I’ve found that this type of bacteria evade a range of proteins and it has led me to seriously question myself and my abilities. But from my own work and that of others we know of one specific protein that’s in place, the one guy who is actually doing his job. And if that protein is there, then this GFP-tagged protein would also be there.

So it was a quiet afternoon when I sat down with the microscope. And I could not believe it. Nothing!
And I mean nothing!
The protein that was so nicely targeting the control particles were nowhere near the bugs. Every scientist I have ever talked to has had this moment. The point during a project that if someone were to walk past the lab they would hear screams. Or possibly crying. Even hysterical laughter.
How? HOW!?!

How DO you do that??
WHAT are you guys doing?

At that moment I realized that these bugs are invisible. Even though they glow so nicely red under the microscope the macrophages can’t see them. This realization does not in any way change my project, but it definitely changes the way I view it. I need to know why the proteins fail to find the bugs.

I seriously need to know!

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