Tag Archives: Inheritance

Research Project Narrated for My Parents

My summer research project, which will span much of the next year, revolves around Classical Ferroportin Disease. Firstly, before explaining the minutia of Classical Ferroportin Disease it is important to know what ferroportin is; ferroportin is an iron transport protein that is responsible for exporting iron out of cells. Classical Ferroportin Disease is a loss of function disease, meaning that a mutation has occurred in the protein that makes ferroportin less efficient [1]. Seeing as though ferroportin is exporting iron out of cells, patients who have Classical Ferroportin disease can get iron into their cells, but their cells struggle to get iron back out of the cells. This ferroportin malfunction results in a net accumulation of iron in cells above what is physiologically healthy; macrophages of the liver and spleen become particularly iron overloaded because they metabolize a lot of iron. The disease can present clinically as anemia because the body is unable to acquire the adequate iron it needs for red blood cell production since the iron is being sequestered in the liver and spleen macrophages with no way to be properly exported [2]. The disease can also cause diseases of the liver such as fibrosis and cirrhosis because iron overload of liver cells is detrimental to liver health and functioning.

It is known that Classical Ferroportin exhibits autosomal dominant inheritance; my summer research project is interested in shedding light upon how Classical Ferroportin Disease is inherited via an autosomal dominant route. There are two models to explain the autosomal dominance that classical ferroportin disease exhibits. One model is a haploinsufficiency model, the other is a dominant-negative effect model [1]. These terms may sound complex but they are fundamentally simple. The haploinsufficiency model can simply be thought of in terms of dosage. When you make a cake the recipe may call for five eggs, if you were to only put one egg into the cake, said cake would turn out abysmally. Haploinsufficiency is exactly the same way; you inherit one copy of ferroportin from each parent. You need two good copies to be a well baked cake and make enough functional ferroportin protein, but if you only get one good copy and one mutant copy then you will be an abysmal cake with not enough functional ferroportin to properly export iron. All in all, in the haploinsufficiency model you don’t have enough functional ferroportin to keep up with the export rates needed to be healthy. The second model, the dominant-negative effect, is a little more complex but still fundamentally simpler than the name implies. This model is best envisioned as an arts and crafts project. Your task is to make a sphere out of two objects and super glue. THE TWO OBJECTS MUST COME TOGETHER TO CREATE THE PRODUCT. In the working art studio you’d be provided with two hemispheres and super glue; you would with ease construct the sphere and happily go about your day. In the art studio run by people lacking infant geometry knowledge, you are provided with one hemisphere, one cylindrical object, and super glue. No matter how hard you try with the materials provided you cannot construct the desired spherical object. Out of frustration you glue the block to the sphere permanently and leave full of rage to throw the mushroom shaped object at a wall.  The complete sphere, representing a healthy person without ferroportin disease, can be made when you are provided with two good hemispheres, one healthy ferroportin gene from each parent. The second art model, where the person is forced to construct a mushroom shaped object, represents Classical Ferroportin Disease via a dominant-negative effect. The person was forced to glue the hemisphere, a healthy ferroportin gene product, to a cylinder, a mutant ferroportin gene product, creating a non-sphere and thus a ferroportin protein unable to export iron. They key distinction between the haploinsufficiency model and the dominant-negative model is that in the haploinsufficiency diseased state you simply do not have enough of the good product, whereas in the dominant negative model the bad product hinders the good product from working all together. Overall my research project revolves around trying to figure out which model Classical Ferroportin Disease follows and my tools to do so are Xenopus laevis oocytes, human mRNA injections, confocal fluorescent microscopy, and scanning electron microscopy. This project falls into a huge sector of molecular biology and physiology that is cellular transport and it will aid in the treatment and understanding of one type of a family of diseases that fall under the name of Hemochromatosis.

Realities of Research

Experimental design is key; hard work pays handsomely in the form of pretty graphs; don’t start to genotype at 3 PM’ and experiments will be repeated a frustrating amount of times until those variance bars look pretty.

The importance of well thought out experimental design became a frustrating reality about 5 weeks into my project. I had been tirelessly performing experiments for weeks in a way that could only be analyzed via a one-way ANOVA. An ANOVA is a commonly used statistical test used to analyze data; all statistical tests require an individualized experimental design in order to be analyzed via a specific test. One day at lunch my PI and I were discussing my progress and he looks at me worriedly and says “How have you been setting up your experiments and how have you been analyzing the data?” He then went on to inform me that my experimental design had a critical weak point and that a one-way ANOVA would not provide the insight needed to make a strong claim on my hypothesis. So the rest of the lunch was spent redesigning my experimental approach so that I could run a two-way ANOVA, yet just another statistical test. This taught me that experimental design is worth troubling your mind over for a long while because good data is meaningless unless it is masterfully collected with a specific statistical analysis in mind.

A lab reality surprise I encountered was how rewarding good data and graphs can be. I grew up playing baseball and soccer and I excelled at them, therefore I know the feeling of hitting a homerun and scoring a goal. They are full body highs encompassed with an adrenaline surge and confidence boost. I was surprised how close to those feelings I got when I got my first very usable data set and graphs. It’s very comparable to sports because you train in much the same methodical way for so long so that when you finally see results it feels amazing. Hard work does in fact pay handsomely with good data and graphs.

Another lab reality is planning your day saves your dinner date. I learned this the hard way multiple times when I started an experiment, genotyping, or prep way too late in the day.  It has become increasingly apparent that planning is your best friend in the lab. Fifteen minutes of thoughtful planning at the start of the day may save you hours each day. AKA don’t hold off on very pressing genotyping until 3 PM unless you plan to be in the lab until 9 PM.

Lastly, a frustrating lab reality is that some experiments will have to be repeated so many times you that start to worry you’ll be running the same experiment with the same experimental groups forever, or even worse you fear they will never give you interpretable data…. gasp. This is a frustrating reality that can never truly be realized until you have suffered first-hand through running the same experiment for weeks on end. It always gets better though; see baseball homerun feelings above.

Life of a Scientist

The most striking part of the day to day of a scientist is how social it is. I always assumed scientists were reclusive and withdrawn. I was wrong, outright wrong. The lab I work in is bustling with life. Intellectual exchange and idea bouncing occurs incessantly as we pipet about running assays. We come together at lunch and effortless fill the air with debate and jovial disputes. But the chit chat goes beyond academics, which I was most surprised about. Beyond bouncing ideas off each other and discussing relevant academic papers, a plethora of enticing conversations about extracurricular activities also buzz loud. We talk about music, the best coffee places, the trendiest foods, sports, and philosophy. Science is inescapably social in a beautiful way. Another thing I love about being a scientist is that your schedule is decently malleable as long as you get plan well. You are able to catch lunch with a friend or leave a little early one day if you make up for that time and work somewhere else; I am trying to get at the fact that science is not a strict 9-5 because as long as you get your work done no one is going to hound you about when you do it. This is a huge plus because it plays very well into an adequate work-life balance.


  1. Hal Drakesmith, Elizabeta Nemeth, Tomas Ganz, Ironing out Ferroportin, Cell Metabolism, Volume 22, Issue 5, 2015, Pages 777-787
  2. Mayr, Roman et al. “Ferroportin Disease: A Systematic Meta-Analysis of Clinical and Molecular Findings.” Journal of Hepatology5-3, 2010
John Bonamer is a senior majoring in Medical Sciences at the University of Cincinnati in Cincinnati, Ohio. He is a UGSRF fellow working in Dr. Bryan Mackenzie’s lab at the University of Cincinnati. John’s Fellowship is funded by the APS. After graduation John plans to pursue an MD/PhD with special interest in Urology.