For MB3006

This is a series of articles that I found useful and/or relevant while evaluating the review article by Thomas Rando. You might also refer to this counter argument published in the same issue of Cell or this proposal of an alternate hypothesis, the Mortal Strand Hypothesis, written by Rando himself in 2013.

Please note that when you are searching for scientific information, you should always try to access the primary research that was done to investigate the question you are addressing. I have provided links to relevant papers below. However, there are also a number of on-line resources from experts that offer clear and concise explanations of these topics, and I’m providing links to a few of these as well. This is NOT license to use un-cited literature or unsupported statements in your own work. Also, please be cognisant of the University’s policy on plagiarism. These links are merely to provide you with alternate learning materials in case the first explanation wasn’t clear.

When searching for scientific literature, I highly recommend that you use Google Scholar, NCBI, or other professional search engines. This will improve the overall quality of your results.

Semi-conservative DNA replication:

A movie showing replication in slow motion, with all the components labelled: https://www.youtube.com/watch?v=27TxKoFU2Nw

Another movie showing replication in 3D, including illustrations of histone and chromatin structures, chromosome segregation, transcription to RNA, and translation to proteins: https://www.youtube.com/watch?v=yqESR7E4b_8

Mutation rates in humans:

Evolution by Douglass Futuyma is available in the UoA library.

An explanation of why mutations occur and why they are problematic from the Nature Education blog (also a great general resource):
http://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-mutation-409

How might you measure mutation rates?
http://jvi.asm.org/content/62/2/558.full.pdf+html
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0043876

How are stem cells different from their progeny?

Cairns 2002 sites this paper describing how bone marrow stem cells are less able to survive base excision repair and these papers demonstrating that they’re more sensitive to mutagens.

What was the 3H-Td experiment and why was it important?

A retrospective by the original first author, Dr. Karl Lark.
A link to the original Lark article (requires JSTOR login).

Early work measured the distribution of markers across generation using density segregation of radioactively labelled DNA. This is a particularly beautiful and important paper. Check it out!

Rando in particular touts these experiments by Potten et al. (See in particular Figure 6 to see what nuclei that retain the radioactive marker look like early in the experiment and after several rounds of division) as being proof of non-random segregation.

What can we learn by looking across multiple species?

Similar findings were reported in the bacterium Escherichia coli, the filamentous fungus Aspergillus nidulans and the plants Vicia faba and Triticum boeticumWhy did they replicate the results in all these different organisms?

I bring your attention to this paragraph in the above retrospective (emphasis mine):

“We soon discovered that established tissue culture lines (HeLa or CHO) had lost this property (Lark et al., 1966). Had we begun with established cell lines, we would probably have concluded that the non-random segregation we had documented in bacteria was not a property of somatic mammalian cell division, and we would have abandoned the investigation. Instead, we speculated that the polyploid nature of these established cell lines had obscured the non-random segregation of diploid chromosome sets. Although the distinction between cell lines that had acquired immortality and primary cell lines with programmed longevity was known (Hayflick and Moorhead, 1961Hayflick, 1965), we had not considered this distinction as a possible explanation for the difference between a primary mouse line and the HeLa or CHO lines.”

What mechanisms might lead to non-random segregation?

Work by Sherley et al. identifying one possible molecular trigger (pay specific attention to figure 1) for asymmetric segregation.

What is p53? More than just an oncogene!

A paper hypothesizing a mechanism and describing possible experiments to test this model.

How persistent is non-random segregation across generations?

Work by Conboy and Rando using multiple markers shows that the less differentiated cell tends to retain the labelled strand.

How have technological advances impacted our ability to address these questions?

Go back over the various links above and look at the years of publication and the quality of the data. What kinds of data are more convincing? Do you think the correct controls have been used in all cases? Do the authors examine a high number of events or just a few? Do you trust their conclusions? Why?

How can we evaluate scientific literature?

How often is a paper retracted, who falsifies data (please note that this article is itself disputed in the literature), why, and what should we do about it?

An examination of how scientists measure whether a paper is good.

Have you found other resources you think would be interesting to discuss? Leave a note in the comments! 

 

 

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Marching for Science

Let me introduce myself. I’m an American scientist living and working in the UK. I’ve been here since 2012, so I’ve witnessed the Scottish referendum and the Brexit vote. During the Ref, I watched my Scottish friends struggle with the decision -to separate deep feelings of nationalist pride from their incredible openness to others, to parse disinformation on both sides about economic consequences and EU status. The night of the Ref, my friends stayed up to count votes or watch the results. I didn’t join in – I had work to do. I couldn’t vote. Given how personal the decision was, I didn’t want to intrude. But I felt the uncertainty on that September night. Would we all wake up to a fundamentally changed Scotland?

Relief and disappointment stuck in the air a month later at an Aberdeen concert when a furious Glaswegian playing Spanish guitar told us all where to get off, as only a Glaswegian can. I laughed sympathetically along with the crowd. The vote hadn’t affected me personally, and besides, it was done and decided. But the passion behind his words was clear: The push for independence was far from over.

When Brexit came around two years later, I was surprised. How often does a country need to hold referenda on state membership, anyway? The British penchant for neologisms made the vote somehow comical. I couldn’t vote, but I educated myself on the history of the movement, the arguments for and against. In Scotland, Remain was the predominant voice. Again, there was the feeling of uncertainty. But we all went to sleep remembering the Ref: sound and fury signifying nothing.

The next morning, my co-workers were in shock. The Scots felt alienated, disconnected from reality, disenfranchised. The Europeans worried about their jobs, their studies, their families, their futures. They all received tailored, reassuring letters from the Principal of the University. I didn’t receive a letter, but I didn’t need one. The vote hadn’t affected me personally. I gave my condolences and went to the lab.

 I’m an American scientist living in the UK. I went home to vote in November. I had learned about absentee ballots destroyed in a fire in North Carolina, and the fact that expat votes aren’t counted until after election day. After Brexit, I didn’t want to take any chances. I put my experiments on hold and flew home. I voted early. I pointed to Brexit and exhorted everyone I knew to vote, to bring a friend to the booths. I knew that feeling of uncertainty.

I didn’t sleep that night. I thought about everyone who would wake up to this new, alternate reality. I thought about the weddings I’d attended for dear friends who might lose the rights they’d fought so hard for. I thought about friends who faced racism daily, even in the protected environment of graduate school. I thought about my sister, at a party when she realized her friends believe women are biologically inferior to men because our brains are smaller and we’re ‘hormonal’.

I’m an American scientist. These days, when people find out I’m American, they all want to know about Trump. When people ask, I pretend to be Canadian. It’s tedious to rehash with strangers who like Trump’s “plain speech” but don’t want to hear about how almost every word is a documented lie. It’s hard to argue with them. He’s not their President. It’s not happening to them, so why should they care about the details? So, I pretend to be Canadian. I pretend it’s not happening to me either. And I tell myself others have it worse, that even though this is our new reality, I won’t have to change my goals for myself.

I’m a Scientist. After the election, I threw myself into my work. I moved to the UK looking for better opportunities. In the US, most scientists don’t gain independence until they’re 43. I didn’t want to wait more than a decade to start my own research, so I left home. I’ve been lucky: the last four years have been the most creative of my life. But I’ve watched so many of my peers here and in the US- people I respect for their ingenuity, their dedication, their sheer brilliance- leave research. Some moved to industry, some to administration. Some to jobs they always wanted. Some were pushed out, digging in their fingernails around the doors closing on them. Some simply disappeared. This is the reality for early career scientists.

Two weeks ago, Trump released his plan to cut the budget of the National Institutes of Health by a fifth. It’s characteristic, but it’s only an exaggeration of a problem we’ve all been fighting for years. Independent scientists have been working at 2003 funding levels for the last 12 years. That’s my entire scientific career. That’s the limit of the careers of so many of my cohort. We’re the lost generation of scientists.

The March for Science is on Saturday. I’ll be at a march in London. I got a special March for Science t-shirt and I’m working on my sign. I’m not as eloquent as that Glaswegian guitarist, but I’m also marching for Independence. I’m marching for my friends who’ve been forced out of careers they trained decades for. I’m marching for the future of a human endeavor that has the potential to save lives, to ease suffering, to teach us about ourselves. I’m marching because there’s work to do. I’m marching for Science. But I’m also marching for myself. I hope you’ll join me.

 

 

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Respiration in action

Project 2: Respiration produces O2 and CO2.

Saccharomyces cerevisiae is such a useful organism because it grows via both respiration and fermentation. During respiration, sugar is converted to ATP, or cellular energy, and CO2 is produced as a byproduct. When Saccharomyces cerevisiae is added to dough, it allows the dough to rise by creating pockets of CO2. What’s more, Saccharomyces cerevisiae is a useful tool for studying human cells because our cells use the same method to produce energy. In this project, we will observe the production of CO2 by Saccharomyces cerevisiae and test different sources of sugar for the capacity to provide cellular energy.

 

Materials:

1 balloon

1 packet of yeast

1 water bottle

Warm water

Potential energy sources: white sugar, brown sugar, barley malt, molasses, honey, agave, stevia , sunflower oil

 

Procedure:

  1. Pour 1/4 packet of yeast to the water bottle.
  2. Add 25 mL warm water.
  3. Add your chosen energy source.
  4. Stretch out the balloon so it is easy to inflate.
  5. Place the balloon over the top of the bottle and observe.
  6. Measure the diameter of the balloon after 5 min, 10 min, and 20 min.
  7. Repeat using different energy sources.

 

Results

What energy sources did you choose and why?

 

Make a table showing the time and the diameter of the balloon for each condition.

 

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Design your own experiment

Project 1, Part 3: Test a hypothesis

You now have several tools to learn about fungi. There are three additional agar plates available for your group. Together, think of a question or questions you would like to address and design an experiment to test them. For example, do you think one of your agents would work better at a different dose? Do you think one of the agents can prevent the growth of your environmental sample? Discuss as a group how you might test these questions, then bring your experimental design to Dr. Ballou and collect the required materials. List the steps of the procedure you followed below and record your results.

 

Materials:

 

 

Procedure:

 

 

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