San Franciscan accents and gene methylation

20191023_145152Isn’t it funny how accents are lost (or gained) over time?

No I have not picked up an American accent, although when I hear myself speak I sound quite bland!

But what I am getting at is that long-lasting effects can be acquired simply due to being immersed in a foreign country: accents are gained without thought, or gained to improve communication (and in the case of the Australian, GET that drink of waterrrrrr). Depending on the individual’s age, accents can be quickly developed: young children develop accents quicker than their grandparents, for example.

OK, so what has this got to do with science and what I am doing over here in San Francisco? Well using the accent analogy, it might be easier to explain how cells can change their gene expression program depending on physical changes to their environment. One theory is that these changes can evoke methylation of genes, and hence provide phenotypic diversity beyond changes to nucleotide sequence. This is because gene methylation is an epigenetic change – epi – above the genes. Typically, methylation at C-G islands, which on the most part, leads to silencing of gene expression.

This process of methylation in response to physical pressure is thought to explain how the cells in your body, which all contain the same set of blueprints (i.e. the genetic material) change into chondrocytes in stiff environments to make cartilage, or change into muscle, or fat cells depending on the physical environment combined with organ-specific factor expression. It also explains the colour variation in calico cats.

Even more cool, DNA methylation has been linked to the formation of memory.

But I digress. Oh yeah, what I am doing here in San Francisco, is to examine gene methylation patterns in cells from the breast, from the ducts that make the milk (epithelial cells) when they are plated on soft and stiff matrices. This is all to understand how mammographic density, which creates a stiffer microenvironment within the breast, contributes to breast cancer. Are the “good” genes that keep cell division in check turned off by methylation? Do methylation patterns change over time in culture? Do cells “remember” the stiffness when plated on a soft surface?

So many questions that I want to find answers for.

For blog
Hot off the press data from UCSF: cells change their actin arrangement when plated on soft versus stiff surfaces. They also change from wanting to link together, to wanting to bind to the surface and move along it (remind you of cancer cells??).

Getting my hands dirty!

20191008_115710Today at the UCSF I got my hands dirty, and built up some muscles filing, sawing, drilling and punch-stamping.

Why? To make polyacrylamide gel-molds custom-made to fit glass coverslips, on which the gel is poured and cells grown. All in the name of optimal image quality.

There is real value in D.I.Y. science, making bespoke apparatus from inexpensive materials which can then be sterilized and re-used. In the image above I have cored out the lids of 15 ml tubes using Kevin’s scissors (shhh), then I used the vice and band-saw to cut the tubes. I also had to use the drill to bore out the bottom of each of the wells of a 12 well plate, to ultimately be able to use the glass coverslip insert for precision optics. The wonderful thing is that what I make I can take!

20191008_151056

Fuiboon (pictured below) showed me how to cast the gels and functionalise the surface using UV – just a UV light box that you use for viewing DNA gels.

20191007_183329  20191007_182149

After observing how the gels are made I will soon be making my own, and investigating the effect soft versus stiff 2D environments have on tumour repressor gene methylation – and maybe a peek into what might be happening in women’s breasts over time when they are dense, and perhaps why cancer arises in these stiffer environments. So exciting!

Continue reading “Getting my hands dirty!”

Perspectives from a breast cancer researcher ABROAD

Why, you might ask, would I want to leave sunny Brisbane, leave my y20191003_175310oung children and husband and step way out of my comfort zone for 6 weeks in San Francisco on my OWN?

I have decided to take on a professional development opportunity, in the lab of renowned mechano – transduction researcher Professor Valerie Weaver, at the UCSF. 

Why should researchers do these things? For me the decision was easy – my boss told me to go. He read my CV and I guess saw that I have potential to be further on that I am – I have had a career significantly interrupted with maternity leaves and moving from Melbourne to Brisbane. He saw that my CV needed a “shot in the arm”. A good boss. Yes I had to get a J1 VISA, yes I had to flit it to Sydney for a day to get this (look Sydney harbour bridge!), and yes I had to arrange someone to cover for my teaching in my absence. So with the full support of QUT behind me, I am here, in San Francisco!

What to pack? Vegemite, Milo, copious amounts of 2-minute noodles (the exchange rate is a killer at 0.68 USD for 1 AUD), your own calculator that you understand, and a smile and open attitude. What Aussies do best. I have discovered that the tearoom chats with the lab members are just as important as the lab training. Here I have learnt about weird and wonderful things – asatellitesttitutes to Trump, American coffee, the cellular glycocalyx… Did you know that every cell has a haze of proteins hanging off the cell membrane – like satellites orbiting the earth – that can interfere and influence its binding to the extracellular matrix? But these chats are where new collaborations are made, pretty much the reason why the structure of DNA was mostly worked out in an English pub over a pint (where women were not allowed – poor Rosalind Franklin).

1973v.3-pub-600w

So here’s to 6 weeks of mind-blowing science, in one of the best labs in the world!

Interview with Lana Schwartz “Lovely Lady Lump”.

Lana Schwartz is a comedian using comedy to spread her lifesaving message for women to have a mammogram. Her show “Lovely Lady Lump” http://www.adelaidenow.com.au/entertainment/adelaide-fringe/comedy/adelaide-fringe-review-2017lana-schwarcz-lovely-lady-lump/news-story/4b25e66ce7f2189fb32bcda4cef48e85 received rave reviews at the recent Adelaide Fringe Festival and she featured in a Channel 10 clip https://www.facebook.com/tenadelaide/videos/1363036930427716/ involving a colleague of mine, Associate Professor Wendy Ingman, who leads informd (www.informd.org.au).

 Curious to know more about this remarkably brave woman who’s breast cancer diagnosis was confounded by high breast density, I asked Lana to do a quick “5/5” – five questions in five minutes session for my blog.

OK Lana, are you ready?

  1. “What is the funniest thing that has happened to you recently?”

I recently went swimming in Blairgowrie beach and as I stepped onto some rocks on the way back in, I thought “gee, they feel a little ‘pinch-y’. Then I thought, “you know, I think they also feel a little move-y”. I looked down to discover that they weren’t rocks, but a massive once yearly migration of thousands and thousands of spider crabs walking into the shallows to moult their shells. I mean, I didn’t know that at the time, all I knew was “OH MY GOD THERE ARE THOUSANDS OF CRABS! THOUSANDS! CRABS!!! I DON’T THINK YOU UNDERSTAND!!! THOUSANDS. OF. CRABS!!!! UNDER ME! AROUND ME! C.R.A.B.S!!!”

Needless to say, I had a small kiniption. Which is yiddish for “a minor (really major) freak out”.

Is that funny? I don’t know. More like a luck thing – just happened to be in the right place at the right time. But it’s all I’ve thought about in the last day.

 

  1. “You’re a new addition to the crayon box. What color would you be and why?”

Yellow! Because all kids draw massive yellow suns in their drawings and I know I’d be used the most and painted with a big happy smile on my face each time.

 

  1. “Why do you feel so strongly about women getting a mammogram?”

Because it saved my life. Literally. It CERTAINLY saved my breasts, that’s for sure. The lump was so deep and the tissue so dense (though I now know that density doesn’t contribute to how breasts feel) that even after the mammo and when we KNEW WHERE it was, it STILL wasn’t palpable. By the time we’d have been able to feel it, it’d be a completely different story – perhaps one without such a happy ending – after all, thanks to a very studious radiographer in 2014, I am healthy enough to step onto a migration of spider crabs in 2017.

I personally believe women with dense breasts should be given the choice to know.

Also, re: mammos – I KNOW that so many women are scared to be screened, because they’re scared they will find something. I can kind of understand that.

But what they don’t understand, is that finding something is a GOOD thing. Because they’ve found it. And if they find it, especially if they find it early, they can do something about it. If they DON’T find it, because you never went, THEN you’re screwed.

So…. go. get. screened.

 

  1.  “What would the title of your autobiography be?”

“Ginge”. Clearly.

 

  1. “This is my first experience being an interviewer, so as my first interviewee, what question should I have asked you?”

Haha! Gosh! Not sure. I get bored answering the same questions over and over, so actually, this was quite a good and different experience. Keep at it!

 

 

Honor Hugo, PhD

ImageHonor worked as a postdoctoral research fellow in cancer cell biology for over 5 years before she took on a 40/40 research/teaching role at the Queensland University of Technology, teaching Human Health and Disease Concepts (LQB281) and Histopathology (LSB566).

Honor has recently formed her own lab group – Tissue Density Mechanics, in which she supervises a Mphil and PhD student. As the lab name suggests, Honor is interested in understanding how mechanical forces within the mammographically dense breast contributes to tumorigenesis. She is working to understand how high breast density contributes to increased breast cancer risk. This ambitious project supported by the TRI-spore Grant (Translational Research Institute) is in collaboration with medical physicists at the Queensland University of Technology and clinicians at various hospitals across Brisbane. Honor has also been supported by the National Breast Cancer Foundation and the Victorian Cancer Agency.

 

Breast in a dish

What if I were to tell you that scientists can keep human breast alive outside the body in a culture dish? Do images of Frankenstein’s monster pop into your head? Well we are learning more about the breast this way include some clues as to what makes up dense breast tissue.

The biggest problem is, a lot of scientific research has been done on cells alone – we take a patients tissue and distill it down into single cells and grow these cells practically forever in the lab. One famous cell line, HeLa, is from a patient Henrietta Lacks, who had cervical cancer in the 1950s. Cells like hers have helped us understand many cell-level processes but how do these cells behave when they are in the body?

This is a very important question, because although we are made up of cells, it is how these cells co-ordinate within their microenvironment that will provide answers to the bigger questions such as how do we cure cancer.

As you know, I work in the field of breast cancer research. Specifically, I am interested in Mammographic Density, also called breast density. I see it as a major problem facing current breast cancer screening programs worldwide, as it can drastically reduce the ability of mammograms to pick up cancer, if it is there. This is called masking and it increases the chance of getting breast cancer. But dense breast tissue can also make cancer grow better, but we don’t exactly know how.

That’s where the breast in a dish comes in. I am involved in this exciting work, where women are graciously providing us with a portion of their breast after surgery*. We do a mammogram on the breast slice and locate the high and low dense areas.

Picture3.png

Picture4.png

Then we cut the tissue up into small pieces..

Picture5.jpg

..and put each piece on top of a small cube of sponge.

 

The sponge is sitting in the same media we use to grow single cells, with some extra goodies added in.

 

 

These pieces of breast, either high or low density, respond to chemical inhibitors in a different way.

Picture7.png

We can see that some chemicals are reducing the density, as shown above. These treatments have specific known targets, so their effect gives us some clues as to what proteins are important in maintaining breast density. This information might also help us understand why cancers grow so much better in this kind of tissue.

*This may be because the woman has an increased breast cancer risk (runs in her family, or has had prior breast cancers removed) and has chosen, with the advice of her surgeon, to have her breast removed, or she may be having her breasts reduced in size.