In the area of scientific research, especially those concentrate in fundamental, mechanistic understanding, the major blockade is definitely looking for funding opportunity. That’s why I heard of the Wallenberg Foundation (in a research group’s prate, indeed) much earlier than recognizing that the Wallenberg Family regimens Swedish finance sector, indirectly contributes to half of the country’s income! It wasn’t until last Friday, that Jubilee Symposium in Molecular Science of Knut and Alice Wallenberg Foundation (KAW100), answers a part of my curiosity.
Knut and Alice Wallenberg Foundation
Founded by the couple Knut and Alice Wallenberg, KAW aims at promoting excellent Swedish research and education since 1917. As the foundation is stepping into its 100th year right now, a handful of symposia covering digital technology, life science, physics and social science were held or are in schedule staring from April across the country.
Of course, I was in the one on 15th September!
My name card. A day starts in Science!
Molecular Life Science Symposium
There are three topics in this symposium, namely proteomics, structural biology and human evolutionary biology. In each session, it starts with the presentation from one of the luminaries in the field about their landmark work, followed by exciting work done by young, local scientists.
After the welcome remarks, Prof. Carol Robinson from Oxford University is the first presenter:
For the general public, Prof. Robinson is perhaps most well known for her title as the first chemistry professor and Oxford, and completion of her phD degree with only two years. But only after studying Biophysical Chemistry and Proteomics, I learn to appreciate her scientific achievement: structural study of membrane protein using mass spectrometry (MS).
Typical membrane-spanning proteins can be receptor, ion channel or energy pump, the thing that they share is that they are big, complex, and oil-liking. With these properties, it is almost predestine that they are extremely hard to isolate and purify, probably defy attempts in crystallization as well. Compared to X-ray crystallization, MS opens a new door to studying of this “rebellious” member of protein family.
But the more intimidating it is, the more determined we are as biologists: recently, an August Science paper promulgates the release of Human Pathology Atlas. It is constructed from the big data analysis of 17 cancer types and 7000+ patience, aiming at addressing the most perplexing questions in cancer biology: How cancers differ in types? How is the same cancer different among individuals? How can people live for years and years after cancer, while the others not? If there is indeed a DIFFERENCE, can we have a personalized prescription?
Most noticeably, this incredible platform is led by Prof. Mathis Uhlén and his team at Department of Biotechnology at KTH and Science For Life Laboratory. That is, they are the people who teach us in class, whom we have seen, talked to, and worked with during summer.
Thanks to the courage of Angelina Jolie for making her medical choice public, the majority is well aware of the linkage between mutation and cancer. Mutation in our DNA sequence, caused by various reasons, provokes a cascade of molecular events that eventually results in uncontrolled cell growth. These mischievous cells, if let go, drains up nutrition from the body, evades major organs, leading to death.
But don’t panic, cancer is not a death sentence: the five-year survival rate can be as high as 95% in melanoma (a type of skin cancers), or as a single-digital number in low-grade glioma (a type of brain tumors). What’s more, for patients who have the same type of cancer, the normalized survival rate fluctuates significantly. We describe this estimation in seriousness and chance of survival as “prognosis”.
“Big data” are the prerequisite of “Big Data Analysis” that is used to build Human Pathology Atlas. First, Uhlén and colleages utilized the two freely available, open access databases, namely TCGA (from NIH), and Human Protein Atlas (from Scilife Lab). These information contains the RNA sequencing profile of healthy and cancer subjects, especially the mRNA expression profile of thousands of genes in various tissue.
You may ask, why RNA, but not other biomolecules were analyzed? RNA, in this case mRNA, it is an “intermediate” between DNA, which writes our genetic code; and protein, the eventual driver of cellular activity. Comparing with proteins, RNA is composed of 4 codes only, it is easy to be deciphered (protein has 20, with complex three-dimensional structure); on the other hand, unlike DNA whose quantity remains constant except for during cell division, the variation in mRNA level dictates how much protein will be produced, thus measuring mRNA level allows us to quantify its protein product in cell indirectly. Last but not least, the advancement of sequencing technology makes this possible!
From the perspective of traditional molecular biology, the so-called “one gene, one protein, one phD thesis”, the scale of bioinformatics analysis is beyond imagination. Different bioinformatics and statistics tool, were used to make sense from these data:
From left to right:
a) Kaplan-Meier survival plot of individual prognostic gene that relates to the length of survival in a patience
b) Heat map showing the pairwise overlapping of prognostic genes between cancer types
c) Integration prognostic genes with human metabolic model
d) Network plot of co-expression genes in a certain cancer type
Some of their results reinforces our current knowledge in cancer biology, while the others open a new door to human curiosity. For example:
1. While there exists no Messiah/Satan (which refers to a positive and negative prognostic gene respectively) for all cancer types in general, we are able to find out prognostic gene(s) for every single cancer type;
2. Just as there is greater variation among individuals than those between countries/races/cultures; variation in gene expression profile across patience for a certain type of cancer supersedes those between distinctive cancer types.
Human Pathology Atlas, as an open-access database and a critical part of the Human Protein Atlas, will prove that our ambition towards a personalized, target-specific treatment of cancer is not a lofty dream. By identifying the role of genes, RNA, proteins and metabolites in the complex human system, hopefully we are gradually filling up the blankets and holes, writing a page from that courage, creativity, and scientific collaboration never surrender in our fight against cancer.
Vacation is not the only option for summer; a number of students from my program Molecular Techniques in Life Science make an alternative decision: a two-month, full-time research internship at Science For Life Laboratory in Stockholm. Among them, a large portion belongs to the annual SciLifeLab Summer Fellow Program (description at end end of this blog), while the rest devote themselves into individual research project.
Now, after spending one month pipetting, culturing tissue or even sitting in front of a computer doing simulation, can they eventually integrate their knowledge from classroom to bench-top, and convert their passion in science to fruitful results in lab? Let’s have a chat with them about their job, their happiness and frustration, pain and gain during their unique summer in research!
Biology? Physics? Chemistry? Despite of its intimidating name, the course biophysical chemistry is one of the most inspiring one I have ever had, and is regarded as the most popular course by two branches of our students. Eager to know what it is?
All you need is Boltzmann
The core concept of the whole course is the Boltzmann distribution, which tells us how likely a state is according to its energy.
The simplest form of Boltzmann Equation
Hmm….how can we link this awkward mathematical expression to biology? Think of this example: inside a protein, atoms are connected with bonds. Some of these bonds are very strong; the others are weaker. Besides bonds, they can also interact with the surrounding molecules, such as water or its ligand/receptor. Imagine that we know the magnitude of all these bonds and interactions, and the temperature is also given. The question is, can we predict what will happen next? Will the protein unfold spontaneously? If yes, how long will the process take? If no, will the protein binds to other molecules, and how long can this binding sustain?
The answer is, yes AND no. Boltzmann distribution says, it is all PROBABILITY that matters.
Expanding the same concept from a single protein to the entire world of biochemistry, biophysical chemistry digs into the universal physical laws under the complex reactions and ever-changing states, acting as a key to unmask them, and make prediction about the future. It is not difficult to imagine how understanding of biophysical chemistry is essential to pharmaceutical applications, such as study of protein-protein docking and ligand screening in early drug development.
Structure of the course
The course was divided into two parts: three hours lecture in the morning and four hours of computer lab, which is a extension of the content in lecture. In order to pass the course, you need to get a “Pass” grade in all the 8 computer lab assignments (Only Pass/Fail for these assignments). The course is graded as A (highest) to F (fail), which is 100% dependent of the four-hour final exam.
After spending the first lecture reviewing the properties of common biological molecules and interactions, we were introduced the Boltzmann distribution at the first lecture. In the computer lab on the same day, we quickly had a feeling of the effect of sampling on this distribution by trying the simulation by ourselves on computer:
Taking more “steps”, closer the results of simulation to prediction
If you are fond of video games, you must have heard about VR, but for an amateur like me, it means simply to put on a special “glasses” with which I can see a virtual world. Therefore, I was extremely excited when I knew that KTH was going to hold theFIRST International Virtual Reality Science Festival from 13 to 14 May. Although it has been a week, this experience is so eye-opening that I hope a recap is never too late!
1. VR Exhibition: Put on your glasses!
The festival is divided into three days, from Friday to Sunday, and into four categories: VR film, lectures, workshops, and of course VR exhibitions from participating institutions. I can’t wait to try VR by myself now!