Happy Day of Immunology!

April 29^th marks the 8^th annual Day of Immunology. It was started in 2005 by the European Federation of Immunological Societies to “strengthen public awareness of immunology as a basis for individual health and well-being”. Almost every time I tell people that I’m studying immunology they have no idea what that means. Since immunology is pretty freakin’ awesome, the Day of Immunology was started to teach the public about what we do. It’s a worldwide event with outreach activities in Europe, North America and Asia. The immunology research group at my university arranged outreach activities at 4 local elementary schools, and I was a team leader and ran a workstation yesterday. I had a lot of fun, and the kids were really interested!

Our session started with a talk about what microbes are. We had a bunch of the giant microbe stuffies that the kids got to check out and share fun facts from the info tags (that’s my collection below – Chlamydia, HIV, white blood cell, red blood cell, egg cell and Ebola(L-R)). Then I gave a talk about all the different kinds of microbes that exist – viruses, bacteria, parasites and fungi. Not all microbes are “bad”, so I made sure to emphasize the good and bad types from each group. I had an argument with one of the professors if there are any viruses that are good – she said no and I said yes. There is this one virus, called gB virus C, that is thought to be good for people that are infected with HIV. People that have HIV and gB virus C remain healthy longer than those people that have HIV and don’t have gB virus C. The virus doesn’t seem to have any effects in healthy people. That makes it a good virus in my books, but she thinks there must be something it does that’s bad that we just don’t know about. Bacteria and parasites/fungi were easier. Bacteria are used to make yogurt and our intestines, mouths, skin etc are covered with bacteria that help keep us healthy. We use yeast to make bread and beer, and penicillin is produced by a fungi. Microbes are everywhere, and they usually are good for us, but some are dangerous, which is why we need protectors.

Our protectors are diverse and have specific roles in keeping us healthy. The first line of defense is the natural barriers. This would be things like skin or mucus that can prevent microbes from actually entering the body. If a microbe passes through the natural barriers, like through a skin, then it encounters the innate immune system. The innate system recognizes pathogen associated molecular patterns (PAMPs), which are commonly expressed on pathogens but not on human cells. A special type of white blood cell called a macrophage patrols the body looking for pathogens. When the macrophage encounters a pathogen it “eats” it. The macrophage, and another type of cell called a dendritic cell, identify any invaders, then travel to lymph nodes (which swell when you’re sick) where they tell the adaptive immune system that there’s an invader. The adaptive immune system contains cells called T cells and B cells. There are a couple different types of T cells. The CD8+ T cells are killers - once they are turned on they go around the body and kill any cells (and only those cells) that are infected with the pathogen. The CD4+ T cells are helpers - they activate the B cells. The B cells produce antibodies which help in the immune response, by increasing efficiency of different immune processes. After the pathogen has been destroyed, T regulator cells turn off the activated T cells. T and B memory cells “remember” the pathogen that they’ve seen so they will react faster if it’s seen again, meaning you won’t get sick at all, or have a much milder case. This is why you only have the chicken pox once. This is also the basis of vaccination – you expose the immune system to a non-harmful “dose” of the pathogen to mimic infection, and your immune system remembers it, so you don’t get sick if you ever encounter the real pathogen. If enough people get vaccinated then you can eradicate a pathogen (like smallpox!).

After the talking bit we split the kids into 2 groups. One group looked at plates of bacteria that we had grown before coming to the lab. We had swabs taken from inside shoes, a piece of hair, cheek swabs, plant water, computer keyboard and lots of other common places. Each plate grew a lot of bacteria, which is kind of gross if you think about it, but bacteria are all around us! The station I was manning was teaching them how to make the plates. I explained how we grow bacteria in the lab and then sent them around the library armed with swabs to set up their own plates to see what grew. One group of boys went to the bathroom and swabbed inside the urinal . . . gross! We brought the plates back to the lab to grow for them, and then will send pictures back to the class.

During all this I was secretly “contaminated” with a glowing (not harmful) germ. It was all over my hands and on the water tube, and could be spread by touching surfaces. You could only see if with UV light, so we checked all the kids after to see who got my “germs”. Almost all the kids had some glowing spots on their hands. With the grade 4/5 class they wanted to keep shaking my hands to see if they could get infected. It was a really effective way to illustrate how easy a cold could spread, and that you need to wash your hands.

It was a lot of fun going to the school, and the kids seemed to enjoy it. Yay Immunology!

C

"Bugs" and Drugs

While I was Twittering away I came across this cool articles about drug resistant bacteria from National Geographic http://news.nationalgeographic.com/news/2012/04/120411-drug-resistance-bacteria-caves-diseases-human-health-science/ Articles about drug-resistant bacteria are fairly common, and we’ve all been told don’t overuse antibiotics because you’ll create a “superbug” that will be resistant to all available antibiotics. In fact, there are some isolated cases that suggest this is already happening for TB, and antibiotics not used properly have taken the blame.

This article could change all that. Microbiologists have found close to 100 types of bacteria that are resistant to modern antibiotics in the Lechuguilla cave system in New Mexico. What is really interesting is that this cave has been completely isolated from humans – a thick dome of rock isolated the cave 4-7 million years ago. The cave was untouched until cavers unveiled it in 1986. Entrance to the cave is strictly restricted, but microbiologist Hazel Barton and her team have been in the cave to sample microbial life. The samples were sent to Gerry Wright at McMaster (Yay Mac!) and tested for signs of antibiotic resistance. The Wright lab was able to grow 93 types of bacteria for testing, and 70% of the bacteria were resistant to 3-4 classes of antibiotics! This is amazing because it suggests that the bacteria naturally have resistance to antibiotics, and the medicinal use of antibiotics hasn’t created the resistance that’s seen now. These bacteria have never “seen” the antibiotics we use. It may be possible that other bacteria that hasn’t been isolated from humans also naturally contained antibiotic resistance, which they passed to pathogenic bacteria. Bacteria that are growing nearby are able to undergo conjugation, which is an exchange of non-essential DNA called plasmids. These plasmids usually contain DNA that codes for antibiotic resistance. Bacteria that were already antibiotic resistance could have given their plasmids to pathogenic bacteria, making them antibiotic resistant too.

Like almost all science, there are some concerns about this research. It’s not known how the antibiotic resistance genes get into the hospital, where they can causes disease like MRSA. It is also possible that what they are observing from the cave looks like antibiotic resistance but is actually something else. Finally, it’s not known how the resistance occurred – did the bacteria generate antibiotics and then the resistance developed, or was the resistance always there and it was just observed when we started using antibiotics? In any case, this finding is pretty cool and leaves open lots of room for future investigations in this cave. Please note – just because these findings suggest new origins for antibiotic resistance in bacteria doesn’t mean you need to change how you take antibiotics. Not all “bugs” need drugs! And if your bug does need some drugs, make sure you take them as prescribed – don’t stop, even if you feel better! Not all bacteria die at the same rate, so you might feel better but could have a little lingering around so make sure you finish your antibiotics course!

C

One drug to cure them....

As a grad student I subscribe to several science journals’ mailing lists. Each time a new issue is published I receive an email giving me a list of the table of contents for that issue. Most of the journals I subscribe to are HIV or virus and pathogen based, but I do get Nature and Science so I can see what’s going on in other fields. There’s some pretty cool stuff being done spanning a lot of disciplines so I find that on Wednesdays and Thursdays (because most of the journals publish these days for some reason) I spend a lot of my “away from the bench” time reading science news. This is going to get worse because I recently joined twitter and have started following Science and Nature, Natural Geographic and WHO (and local traffic!).

There was this really cool article in Science recently about a new cancer drug that can “cure” multiple types of cancer (The CD47-signal regulatory protein alpha (SIRPα) interaction is a therapeutic target for human solid tumors. Willingham et al. PNAS 2010 www.pnas.org/cgi/doi/10.1073/pnas.1121623109. To appreciate how amazing this is, you first need to appreciate how complex cancer is. There are many factors that make cancer treatment complicated. The first is the variety of cancers that are present – liver, lung, bone, blood, to name a few. Each cancer affects a different part of the body, which means that different types of cells are involved, which is why you typically need different treatment plans for different types of cancer. So, you’ve started with one disease that has different types – if that wasn’t complicated enough to treat, each cancer is different, just like each person is different. Cancer develops when your cells have mutations that prevent them from behaving normally. There are several different tumour suppressor proteins that keep your cells from growing uncontrollably, which is a hallmark of cancer. Think of when you have a cut that has healed – new skin cells grow to cover the cut, then when the cut is healed no more new skin cells are grown – you don’t need them and your skin cells are programmed to know when you have “enough”. In cancer, the cells don’t know when to stop growing. Since this is very important to prevent, there are multiple “checks” in place. Each tumour that develops in different people, even if it is in the same organ, likely has a different set of mutations that lead to it being able to grow. Different mutations react to treatments in different ways. This is why two patients that both have the same type of cancer (ex. Breast cancer) could have different treatments.

In addition to these problems, cancer cells are usually “invisible” to the immune system. The macrophage cells of the immune system monitor the body for cells that aren’t normal (cells infected with viruses or bacteria, or cancer cells in some cases) and “eat” the unhealthy cells. Cancer cells can “hide” themselves and the immune system doesn’t destroy them. This allows the tumor to grow with no interference.

Several research groups have shown that the expression of a protein called CD47 on the surface of healthy cells interacts with a protein on macrophages called SIRPα, and this give the macrophage a “don’t eat me signal” so the healthy cell survives.

Willingham et al collected ovarian, breast, colon, bladder, glioblastoma, hepatocellular carcinoma and prostate tumor cells from patients. They examined the tumor cells and found that CD47 was expressed on almost all the tumor cells. The tumors expressed CD47 at levels 3.3-fold higher than what is seen on healthy cells. This means that the tumor cells have really high levels of the “don’t eat me” signal, which may be why the immune system hasn’t destroyed the tumor.

I thought there next step of experiments was very interesting. The researchers wanted to see if using an antibody to block CD47 (so it couldn’t interact with SIRPα) would allow the macrophages to eat the tumor cells. A special microscope with a camera is used to watch macrophages eat tumors. They found that if they treated the tumor cells with an antibody against CD47 the macrophages were now able to eat the tumor cells. If they didn’t add the antibody, nothing happened to the tumor cells. The next part was really cool – they created xenograft tumors by taking patient tumors and putting them into immunodeficient mice. Once the tumors were established they treated the mice with the CD47 antibody. Tumor growth was inhibited in these mice, and they had longer survival. In some mice, the tumor was actually eliminated. They repeated these experiments in immunocompetent mice, and the same thing was found.

This study is pretty cool because they show that they can treat and even eradicate different types of cancer in mice, using the same treatment for each cancer. A finding like this could revolutionize cancer treatment. While this study is a sign of hope in the cancer research field, it is only one study. More information about the mechanism of exactly how this works, and more studies will need to be undertaken before clinical trials can begin. But it is definitely a step in the right direction for cancer treatments!

C

Caramel Apple Invention Cupcakes

I was making my standard vanilla cupcakes (from scratch) over the weekend and decided to spice things up. I have come to the realization that I shouldn’t buy bags of apples because I either always pick a bag of apples that are mostly bruised, or somehow am unable to transfer the apples safely to my apartment. As a result I have a drawer full of apples that are only suitable for baking in my fridge. I was going to make apple cinnamon vanilla cupcakes, but I’m not that big of a fan of cinnamon and didn’t want to over-add cinnamon and then not like the results, so I decided to use some caramel sauce instead. I made the vanilla cupcakes as the recipe states, then added 2 peeled apples and 2 tablespoons of caramel syrup. The resulting invention cupcakes are ok, but I’d definitely make some changes for next time. I think I’d replace the vanilla completely with caramel syrup and add another apple. I’d also make sort of an apple crisp topping (minus any cinnamon) and add it on top with a drizzle of caramel sauce. The results of this sounds really good to me! I’ll have to post an update later - with a recipe and picture if they’re good – because I need to eat my first attempt at caramel apple cupcakes first!

C

Homemade Yogurt? Not a cost saving tip I want.

After a day in the lab I like to have a granola bar before I head to my car for the long drive home. I thought I’d try making my own to lower the sugar and add whatever I wanted to them (raisins = evil). I came across a recipe on pinterest (pinboards – something else I love) and linked to a blog to check them out. The granola bars were pretty tasty, and I’m still working on how I like them best (dark chocolate, pomegranate craisins, almonds, pumpkin seeds and sunflower seeds so far). The blogger had several other “make your own” recipes to help cut down on food costs – a must for a grad student! Some recipes seemed good, some like too much work, and I found one that I really really did not like – homemade yogurt. Her rationale for making her own yogurt was based on cost savings per year. I figured out that it would cost me $3 (plus time) to make my own yogurt each month, or $5 to buy a month’s supply of yogurt from the grocery store, if I continually bought it on sale. Net savings would be $2 a month – not really worth it in my opinion – you are growing BACTERIA AT HOME for YOUR CONSUMPTION. As someone that works in microbiological research I regularly grow several types of bacteria or mammalian cells in the lab. Do you know how easy it is to get some sort of contaminating bacteria (or fungus) in with your cells? There have been days that I have done nothing different, washed my hands, wore gloves etc and I find a new type of bacteria growing with my cells. I have no idea how it got there, and most of the time I can’t even see that there is a problem until I look under the microscope. With so many microbes that live on/in the average human, I wouldn’t want to risk introducing an unintended bacteria into my yogurt culture. Sure, there are precautions that she takes to prevent this, but is it worth the risk? And what if I make my yogurt and it smells “bad”? (a good sign of a contaminating bacteria) That entire batch has to be thrown out and started over, raising the cost of making the yogurt above the cost of buying it. In my opinion there are too many risks to making your own yogurt. I would rather spend the extra $2 a month on yogurt made by the “pros”. I’d can save $2 elsewhere and be confident that my yogurt doesn’t contain any extra, potentially harmful, bacteria.

C

Welcome!

Welcome to Cupcakes and Science. Although these topics don’t really have much in common, they are two things that I really like so I thought I’d combine discussions on both of them to create a blog. Some days I will be posting about new recipes or decorating tips from my adventures in baking, and other days it will be posts about cool science news.

A bit about me . . .

I like to think of myself as a scientist, but truthfully I am just a PhD student in Microbiology and Immunology. I love learning about infectious pathogens (viruses and bacteria) and how they infect and interact with humans. I am currently trying to use genetically modified bacteria to prevent HIV (and HSV) infection in hopes of developing a gel women can use to prevent HIV (and HSV) infection. It’s really interesting and, if successful, could have huge impacts, particularly in developing countries. I am proud of my academic achievements, so I will add that I received an MSc in Immunology, where I did research on cancer immunobiology, and a BHSc (Hons). I’ve been in school non-stop for 22 years now, and have 3-5 more years to go before I finally graduate. As a PhD student most of my time is dedicated to lab work and research, with no actual class time after my first year.

 

I’ve always liked baking goodies, and I liked cupcakes before they were cool :p I mean, what’s not to love? They are basically individual cakes and there are so many possibilities with them – toppings, decorations, flavours. I have delicious recipes for the basics - homemade chocolate or vanilla cupcakes - and have been trying to become artistic to decorate them. I got a page-a-day cupcake calendar for Christmas, which provides me with 6 new cupcake recipes each week. With all these possibilities, I’m about to go cupcake crazy, and you get to tag-along!

C