How immune cells communicate with our gut microbiome; Dr Dimitra Lamprinaki’s fellowship
4th October 2024
We catch up with Dr Dimitra Lamprinaki who is starting a new Quadram Institute Fellowship focused on discovering how our gut microbiome communicates with our body
“Our gut is populated with trillions of microbes, collectively known as the gut microbiota. In a healthy state our body helps to regulate the gut microbiota.
We often see the response in our bodies to gut microbiota, but we don’t fully know what is interacting on the cell surface level. Innate immunity is the first defending barrier between us and microbes, from cell to cell. It intrigues me.
I’m interested in understanding the mechanism of how gut microbiota interact with a protein superfamily that is found in our bodies’ immune cells.
Are lectins a link between our immune system and gut microbiota?
The proteins I’m interested in are called lectins. Some lectins are found on the surface of important immune cells in our body. Lectins is a broad term that describes proteins that can bind to sugars.
We know that lectins on our immune are linked to either increasing or reducing inflammation. We also know that gut microbes are coated in sugars.
My hypothesis is that some lectins stop inflammation getting out of control in our body, and certain gut microbiota coated in specific sugars interact with these lectins to maintain a healthy state.
The specific lectins I’m interested in are called Siglecs (Sialic acid-binding immunoglobulin-like lectins) and are found mostly on immune system cells. Siglecs are known to inhibit inflammation.
A few researchers have looked at how disease-causing microbes interact with Siglecs. But nobody has looked at how Siglecs interact with friendly microbes.
I am hoping to identify novel interactions and something new about how our immune system is regulated in a healthy state.
I hope that by understanding how a healthy microbiota is maintained it will help develop therapeutics to prevent a disease state.
A career in science from cancer microbiology to flow cytometry
I’m very curious. The unknown has always intrigued me and I was drawn to science.
I joined the Institute of Food Research, the predecessor to the Quadram Institute, for my PhD where I studied lectins and microbiota in cancer progression’.
I started by screening the interaction of cancer associated bacteria with a wide range of cancer inducing proteins. Through these experiments I found that Siglecs bind to colon cancer associated bacteria called Fusobacterium.
After my PhD, I went to the University of Alberta in Edmonton in Canada to join researchers also working on Siglecs. Their research focused on the role of Siglecs in the immune system.
There are fifteen Siglecs and they coat different immune cells. In Edmonton I learnt more about their host interactions inside the human body. I liked Siglec biology even more.
After my postdoctoral position in Canada, I returned to the UK and joined the Quadram Institute. I joined to work as the manager of the Flow Cytometry facility. Flow cytometry allows us to analyse and sort single cells based on their size and characteristics.
Currently, I am also working on a Bowel Cancer UK funded project to identify Siglecs and antibodies in the blood that are linked to microbes associated with colorectal cancer.
The idea is that we might be able to identify markers in the blood for colon cancer. The hope is that if you have the blood and faecal (FIT) sample data, you can reduce the number of false positives so less people have an invasive colonoscopy unnecessarily.
Studying lectins in a healthy gut microbiome
In my fellowship I’m linking together lots of areas that I know and have experience of, on a project that will hopefully be helpful and insightful.
First, I’m going to isolate the microbial cells from colon tissue and faecal samples.
We have cell lines where we express just the Siglec protein, so we have the Siglec protein itself. We can then tag the Siglec, and incubate with tissue microbiota to see which interact.
It’s nice in my fellowship, because I’ve kept collaboration with researchers from the University of Alberta. Through BBSRC’s International Partnership funding I have been to Canada to learn more techniques on how to knock down the Siglec on the immune cells. The idea is that in the model I’ll have the cells that express Siglec but also the knocked down cells that don’t, so I will have a negative control.
Using my expertise of flow cytometry, I will have the microbiota and the Siglecs and put them together. Using the facility I will identify the microbiota that bind to Siglecs because we can sort them in the machine.
Then using the sequencing facility here at the Quadram Institute I will characterise the specific bacteria, so I can find the signature of a healthy gut and which microbes interact with Siglecs.
I’ll be looking at fungi and viruses too, as well as bacteria, to learn about the whole microbial community. That could involve other expertise here at the Quadram Institute with other researchers who focus on viruses and bacteriophages. At the moment, we know very little about how viruses and fungi interact with Siglecs.
Through my fellowship I hope to explore in more depth the mechanism of how Siglecs and microbes interact. I’m going to use the gut-on-chip models we have at the Quadram Institute. The gut on chip technology can simulate the conditions inside the human body. I hope to identify immune responses to understand better the mechanism of how Siglecs and microbes interact.
I’m so excited to understand the first interaction between gut microbiota cells and human cells.
Although my fellowship is focused on the healthy state, down the line it could help us understand cancer and other disease states too.”
Related People
Related Research Areas
Food, Microbiome and Health