Monthly Archives: January 2016

Members

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council_2016

ILS Student Council mailing list
ils-council at helsinki dot fi
Contact for joining the council and for general information about what we do

Kornelia Mikula
kornelia.mikula at helsinki dot fi
Contact for joining the council and for general information about what we do

Gergana Gateva
gergana.gateva at helsinki dot fi

Heidi Haikala
heidi.haikala at helsinki dot fi

Elina Pietilä
elina.a.pietila at helsinki dot fi

Sigurdur Gudmundsson
sigurdur.gudmundsson at helsinki dot fi

Tuomo Hartonen
tuomo.hartonen at helsinki dot fi

Maarja Laos
maarja.laos at helsinki dot fi

Sawan Jha
jha.sawankumar at helsinki dot fi

Kul Shrestha
kul.shrestha at helsinki dot fi

Alok Jaiswal
alok.jaiswal at helsinki dot fi

Mridul Johari
mridul.johari at helsinki dot fi

Lydia Sagath
lydia.sagath at helsinki dot fi

Behnam Lak
behnam.lak at helsinki dot fi

Former ILS Student Council members

Markku Hakala

Heini Hakala

Kaisa Rajakylä

Rita Cerejeira Matos

Jaakko Lehtimäki

ILS PRISM

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Welcome to ILS PRISM. We are delighted to inaugurate the launch of a blog space from the ILS Doctoral Program. We hope that the blog will trigger the electrical impulses in the readers’ brain to be more inspired about science and also communicate it.

The ILS PRISM will serve as a space for:

(i) creative outlet in the form of writing or other medium of communication for ILS members
(ii) reporting news of ongoing activities at ILS
(ii) sharing some of the best scientific writing or related contents available in the web to read, watch, listen

We would like to invite the students and PIs in the ILS community to send your write-ups, and also of others that you read and think they are worth sharing to a wider community. We would be pleased to post your blog material if you are into blogging.

This blog is maintained by Alok Jaiswal and Mridul Johari from ILS Student Council. For more information email us at:

alok.jaiswal at helsinki dot fi
mridul.johari at helsinki dot fi
ils-council at helsinki dot fi

TOM – 03.02.2016

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Group Factor Analysis

Presented by:  Suleiman Ali Khan, Post-doc, Group Aittokallio, FIMM

http://users.ics.aalto.fi/suleiman/

A key underlying problem faced by informaticians in general and computational biologists in particular is to identify the dependencies between one or more datasets. Recent advancements in machine learning have led to creation of a series of methods that could identify statistical patterns shared between multiple datasets as well as enumerating those specific to anyone. ‘Group Factor Analysis (GFA)’ is a key tool that has recently come up to address these challenges, and in the first session of TOM I will give an overview GFA and some of its practical use cases in bioinformatics and computational biology.

For more reading:

http://bioinformatics.oxfordjournals.org/content/30/17/i497.full.pdf+html

http://research.cs.aalto.fi/pml/online-papers/khan2014ecml.pdf

http://jmlr.csail.mit.edu/proceedings/papers/v22/virtanen12/virtanen12.pdf

TOM Schedule

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This is a tentative schedule for spring session 2016

Date Presenter Title of presentation
03.02 Suleiman Ali Khan Group Factor Analysis
17.02 Riku Katainen Analysis and visualization tool for next generation sequencing data
02.03

Arvydas Dapkunas

Ville Rantanen

Analyzing kidney development

NiceCSV
16.03 Simon Anders DESeq
30.03 Liye He

Phylogenetic reconstruction of cancer evolution using LICHeE
12.04 Svetlana Ovchinnikova Metric learning approaches
 27.04 Mikhail Shubin Data visualisation
11.05 Christian Benner  FINEMAP: Efficient variable selection using summary data from GWAS
25.05 TBD

 

Meet a Bioinformatics student who met “30 Nobel Laureates”

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Original blog link:

Meet a Bioinformatics student who met “30 Nobel Laureates”

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  • The Lindau Nobel Laureates meeting with Prof. Walter Gilbert who developed the DNA Sequencing methods
  • Camel ride at the Canary islands
  • Reindeer Safari in Lapland
  • My Master’s Graduation ceremony

Let me first start with my childhood. I was born in Madurai and brought up everywhere. As my father was a bank employee, he used to get transferred every 2-3 years and we had been relocating with him. I studied in many different schools all over Tamil Nadu, which indeed gave me an opportunity to mix up with people from diverse backgrounds. Thanks to my mother, wherever I studied, she encouraged me to participate in all the competitions, which helped me to boost up my confidence.

When I was in my 10th class, we had a discussion about “Which group to choose and where to study?” Well, the direct questions were, if I should become a doctor or an engineer. I actually liked both computer science and Biology. Since we have a doctor (uncle) and 3 pharmacists (grandfather, uncle and aunt) in our family, everyone motivated me to choose biology. After endless discussions, I decided to study biology. So, my fate was decided then and everyone was looking forward to seeing me as a doctor. I was putting my utmost efforts to become a doctor. Unfortunately, my board exam marks were not as good, as I expected. Well, I secured 97.5, but the cut-off that was needed to get a MBBS seat under the government quota was 98.5 back then. Many of my relatives told me to get into some engineering college. Just because, I didn’t get a medical seat, I didn’t want to choose some random course and be happy with my life. My father always says, “Never do something that you don’t like”. I was very stubborn in my decision.

I took a break, stayed home for 1 year and wrote all possible medical entrance tests both at the state and All India level. I also used this time efficiently to interact with as many doctors and engineers as possible. One thing I figured out from their conversations was “They decided to become an engineer or a doctor, just because their parents wanted them to do so or their friends and relatives motivated them or they didn’t know what to do and chose to become an engineer”. After hearing their stories, I decided that I don’t want to be one among the crowd and I should do something different. At that point, I was happy that I didn’t get a medical seat and I didn’t choose some random engineering course that I was not interested in. Just to warn you that this is not the overall statistics. It is my perspective based on the few conversations; I have had with the engineers and doctors. I explored all possible career options with the help of resources that were available online and in newspapers. One morning, when I was having coffee with my father, he told me that he came across a course called “Bioinformatics – Solving problems in Biology with the help of computers”. I got so excited, as I wanted to study both biology and computer science. When I looked into career options for this course, I didn’t find many job opportunities in India. Since I liked the course curriculum, I opted for doing B.Tech Bioinformatics in SASTRA University. This is how I ended up in Bioinformatics.

When you have a passion for something, you will definitely excel in what you are doing. I was very happy during my B.Tech and kept my eyes open looking for opportunities. I went to many conferences, visited industries, attended many research trainings and worked as a summer research fellow.  I enjoyed all these experiences and wanted to be a Master in Bioinformatics.  I was in a dilemma with the questions popping up in my mind, “Where to do Masters? How to promote my career further ?”

When I was doing my 3rd year B. Tech, I got a chance to attend a Career Abroad program conducted by Mr.Sivakumar and Ms.Savitri in SASTRA. That was a life changing experience and I got to know about the Masters’ programs in many different universities across the globe. I was so excited and started preparing for GRE. In the mean time, I got placed in an IT company. I didn’t want to take up the job because I wanted to do masters. But then, the financial situation was not so favorable to start masters immediately after my Bachelor’s degree. Even my parents advised me to take up the job to gain some experience. To be frank, they were afraid to send me abroad initially. After all this drama, I started working with the intention that I will quit after 2 years. Though I took up the job, I used to think every single day that I should study Bioinformatics and shouldn’t work as a software engineer. I couldn’t handle this after 1 year. I made a bold decision to quit my job and apply for Masters.

Though my initial plan was to do my masters in US, I got to know from my friends that there are many exciting opportunities for Bioinformaticians in Europe. So, I sent my applications mainly to the universities in Scandinavia and Switzerland.  I had to wait for 6 months to get the decision from the universities.  I had no clues what to do during these 6 months and approached Shiva sir about getting a position in Trichy Plus. He immediately agreed and I started working there. I would say that this was one of the best experiences in my life. I really enjoyed interacting with students and helping them with their career growth. In fact, this job made me realize that communication skills are my strongest assets. Thanks to Siva sir and Savitri mam for being the mastermind behind the success of many students from Trichy. I feel so great to be a part of TRICHY PLUS.

Finally, after waiting for 6 months I got the admission letters from all the Universities, I applied. I chose University of Helsinki over other Universities because the Masters program is really flexible in Finland i.e you are free to do any course you like during your Masters, including the ones from other departments. Moreover, the quality of education is really good in Finland and it is free. Having all this in mind, I took the major step forward to accept my admission and moved to Finland.

Finland is very different from India, both climate-wise and culture-wise. I was shocked in the beginning. But then within a year, I got adapted to everything with the help of my friends.  Gradually, things turned out good and I got an opportunity to do my Masters thesis in a Pharma company, where I worked on developing new computational methods to assist the design of selective drugs for cancer targets. Overall, I was very happy with my research experience and wanted to continue further.

With the support of my research supervisors, I started a PhD in Computational Drug Discovery at the University of Helsinki in 2012. Even though I have been to many conferences during my PhD, attending the Lindau Nobel Laureates meeting, where I got an opportunity to meet “30 Nobel Laureates” in the field of Medicine and Physiology was a life changing experience. The mind-blowing speeches by the great legends changed the way I think and do research. This was indeed the happiest and the best moment in my life. Though my PhD journey has been quite successful so far, I faced many challenges.  The moment I think that my research is contributing to improve the strategies used in drug design, all these problems disappear like passing clouds.  As a PhD student, I think it’s just the beginning. I am looking forward for much more challenges and opportunities.

In addition to doing research, I have been traveling quite a lot for the past 5 years.  Every trip has been a memorable one, because of the interesting personalities I met during these trips. You learn only by experiencing things and meeting people. Whenever you get a chance to travel, utilize it.

Something that I learnt during these years, “Always pursue your passion. Success will follow you”. Whenever you are confused about making a decision, take a short break, devote some time for yourself and do what you think is right. Sometimes, it is good to satisfy others. But it’s your life. You need to decide, what is good and what is bad for you.

You can contact Vigneshwari at vignesh.bioinfo@gmail.com

https://fi.linkedin.com/in/vigneshwari-subramanian-10931749

Farming opioids from sugar

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Metabolic engineering of yeast cells to produce pharmaceutical and natural products has been around for some time, notably used for production of a precursor metabolite of the widely used antimalarial drug artemisinin. Galanie et al. [1] demonstrated that metabolic pathways from other organisms can be reconstructed in yeast to synthesize complex natural products such as opiates and their opioid derivatives. Opioids are widely used as painkillers and also have diverse effects on the human body. The authors engineered yeast strains to express and knockout more than 20 heterologous genes, from organisms like plants, rats, bacteria and even yeast to convert central metabolites to thebaine, a precursor for codeine – the most commonly used opiate. Biosynthetic production of natural products is tackled by modularizing the genetic circuits to produce intermediate metabolites. The authors (i) first created a module to produce (S)-reticuline from tyrosine; (ii) convert (S)-reticuline to (R)-reticuline, a key step in the pathway; (iii) optimized the conversion of (R)-reticuline to thebaine. Enhancing the production efficiency by diverting metabolic flux through the existing modules and additional pathway engineering could scale-up the process and make it possible for commercial production.

  1. Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD. Complete biosynthesis of opioids in yeast. Science. 2015 Sep 4;349(6252):1095-100.

Replacing yeast genes with human genes

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Consider a yeast cell and a human cell, what will happen if the genes that are essential for survival of yeast are substituted by their human orthologs? Coding sequences of these genes have diverged almost a billion years ago, but have their functions? Kachroo et. al. [1] found almost 50% of essential genes, out of nearly 400 chosen for study, can be replaced. To the question of what factors determine replaceability, they found although sequence similarity explains some aspect of it, the major determinant seems to be the biological pathways to which these genes belong. Genes making protein products having enzymatic role in metabolism, sterol biosynthesis and part of the proteasome are more amenable to humanization compared to genes involved in DNA replication, repair or cell growth. This might indicate that the machinery for some biological processes/modules have evolved very differently in the two organisms, whereas some of them have been kept as they are. What could be the reasons for slower evolution of those biological modules?

  1. Kachroo AH, Laurent JM, Yellman CM, Meyer AG, Wilke CO, Marcotte EM.
    Evolution. Systematic humanization of yeast genes reveals conserved functions and genetic modularity. Science. 2015 May 22; 348(6237):921-5.

Can we drive malaria away with gene drives?

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The dreadful effects of malaria need no recalling. One strategy to counter it is by creating mutant mosquitoes that are resistant to the parasites. However, the bottleneck has always been to ensure that the mutant mosquitoes should also spread in the wild population rapidly. Gantz et. al. [1] exploited the genome editing power of CRISPR to create a method for mutagenic chain reaction (MCR) [2] in mosquitoes. MCR technology allows us to create homozygous loss-of-function mutations in the germ line of the host organism that spreads rapidly through its offspring. Inserting mutations in two genes that cause resistance to the malarial parasite, the authors engineered a gene drive that passed on the modified homozygous genes to 99% of their offspring. Gene drives based on CRISPR-Cas9 have the potential to rapidly spread through the wild population. However, a lot of work is still required to assess its stability when introduced in a gene pool and developing human regulatory control before the powerful technology can be taken out of the lab.

  1. Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM, Bier E, James AA. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc Natl Acad Sci U S A. 2015 Dec 8; 112(49):E6736-43.
  2. Gantz VM, Bier E. Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. Science. 2015 Apr 24;348(6233):442-4.

CAT tails and tales of truncated protein synthesis

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Just like any other man made machine, the natural protein synthesis machinery a.k.a. the magnificent ribosome, also fails at times. Stalling midway between its duty of forming peptide bonds between various amino acids, it produces truncated/nascent proteins that are unwanted by the cell. The cell has therefore developed a mechanism to get rid of these toxic truncated proteins. Shen et. al. [1] found that ribosome gets partially disassembled after stalling and also looses the mRNA, followed by recruitment of Ltn1p and Rqc2p to the subunit having the nascent peptide. Ltn1p binds to the side of the ribosome where proteins are spewed out and tags them with ubiquitin, a marker for destruction. Also, Rqc2p interacts with transfer RNA binding sites and stitches only alanine and threonine to the incomplete protein, producing a CAT tail (i.e. carboxy-terminal Ala and Thr extensions). CAT tails may induce heat-shock response to ensure degradation of the truncated proteins and also protects the cell from their toxic effects. In short, when the ribosome fails, the cell still manages to sustain protein synthesis even in the absence of any genetic instructions and targets them for recycling.

  1. Shen PS, Park J, Qin Y, Li X, Parsawar K, Larson MH, Cox J, Cheng Y, Lambowitz AM, Weissman JS, Brandman O, Frost A. Protein synthesis. Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains. Science. 2015 Jan 2;347(6217):75-8.