PhageShift: A new take on bacterial infections.

Creative Technology

Help us design a new effective method to target bacterial infections using the antibacterial properties of phages.

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IISc Bangalore iGEM Team

About the Fundraiser

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IISc iGEM 2018 is the official team for the International Genetically Engineered Machines (iGEM) competition representing Indian Institute of Science, India’s premier research Institute. We are a team of more than 20 undergraduate students from different parts of India and disciplines of science coming together to help overcome deadly bacterial infections which have become resistant to antibiotics, by using and improving bacteriophages. 


Since the discovery of antibiotics by Alexander Fleming in 1928, they have taken the world of antibacterial therapeutics by storm owing to their efficacy and wide spectrum of treatment. However, the increasing risks of development of antibiotic resistance are now being realized. Uncontrolled use of antibiotics in medical, poultry and agricultural sectors is leading to appearance of strains that are resistant to last resort antibiotics like carbapenem and polymyxins. This slippery path could soon result in "Superbugs", which are resistant to all antibiotics, thus taking us back to an era where a simple wound could be fatal. This isn't mere fear mongering, the threat of antibiotic resistance is very real and near. Here are few news articles which inspired this project:

With PhageShift, we aim to shift the paradigm of bacterial infection treatment from antibiotics to phage therapy - a technique that was widely used between 1920 and 1940. Bacteriophages are natural enemies of bacteria and are present almost everywhere bacteria exist, from sewers to lakes. The hype created with the discovery of antibiotics put phage research on the back burner; but the rise of antibiotic resistance is leading the scientific world to once again look at Phage Therapy as a viable option. Their extreme specificity is a boon for treatment. A phage that targets a particular bacterial species will not infect any other cell, and doesn't disturb the body's ecosystem. This is especially beneficial compared to antibiotics which often cause a variety of unpleasant side effects.


Image of plaques produced by phage Rogue1 on culture plate containing E. coli O157, an infamous pathogen that causes dysentery in humans. 

(Casey, Eoghan, Douwe van Sinderen, and Jennifer Mahony. "In Vitro Characteristics of Phages to Guide ‘Real Life’Phage Therapy Suitability." Viruses 10.4 (2018): 163.)


The development of this technique has been severely limited due to few research groups working on it and a lack of complete understanding of the mechanism of action of bacteriophages. None of the phage therapy methodologies utilized nowadays try to address the extreme evolvability of phages against bacteria that have grown resistant. Our project this year aims to alleviate these problems by utilizing a four pronged strategy to target severe antibiotic resistant strains, especially our primary target - colistin resistance.


Colistin resistance - An imminent danger

Colistin is an important antibiotic given as a last resort drug to patients with a gram-negative bacilli infection. The use of this antibiotic is avoided until the condition of the patient is extremely serious because of its severe kidney toxicity. Recently, K. pneumoniae strains with colistin resistance have been identified in regions of china and southern India. This is alerting because now, even last resort antibiotics face the risk of becoming obsolete.

We are trying to fight against the spread of colistin resistance using two approaches - PACMAN and CARE.


PACMAN (Phage Antibiotic Complementarity Mediated Antimicrobial Network) involves the genetic engineering of a phage such that the pathogen can never development resistance against both antibiotic and phage together. In such a case, administration of both antibiotic and phage will allow successful treatment.




CARE (CRISPR-Cas9 Assisted Resistance Elimination) utilizes phages to deliver the well known CRISPR system to target and degrade the mcr-1 gene which has been found responsible for conferring colistin resistance to these bacteria.

Fighting Phage Resistance

Finding phages against a pathogen is a relatively simple process compared to finding antibiotics. However, phage therapy faces the same obstacle as antibiotics: development of resistance. However, phages have the incredible ability to evolve if their host cell develops resistance. This evolution is extremely slow and requires multiple generations of phage progeny to appear before successful targeting of the new resistant bacteria. This timeframe may not be ideal in cases where immediate treatment is required. This is where our APES component of the project comes in.

An automated hardware project, APES (Accelerated Phage Evolution System) will allow for rapid development and selection of phages which have evolved to overcome the resistant bacteria. This project will be really handy to ensure Phage Therapy does not face the same challenge in the future as antibiotics do currently.



Preventing Endotoxin Release

One of the problems with both antibiotics and conventional phage therapy is the fact that they lyse (fragment) the bacteria after killing them. A normal, healthy person may be able to handle it, but this endotoxin release can be very dangerous for patients with high MOF scores or peritonitis. To ensure that Phage Therapy is accessible to this group too, we have designed the next component of our project. 

PAIR (Phage Assisted Immune Recruitment) deals with the problem of endotoxins by engineering lysis deficient phages that put the pathogen in suspended motion. It then recruits the bodily immune cells to engulf them, preventing release of endotoxins into the bloodstream. 





About iGEM


The iGEM competition is an annual, worldwide, synthetic biology event aimed at undergraduate university students, as well as high school and graduate students. For over 10 years, iGEM has been encouraging students to work together to solve real-world challenges by building genetically engineered biological systems with standard, interchangeable parts. Student teams design, build and test their projects over the summer and gather to present their work and compete at the annual Jamboree held in Boston, USA.

iGEM 2016 saw over nearly 5600 participants from over 40 different countries participating at the annual Jamboree at Haynes Convention Center, Boston (USA).

About the team

The undergraduate team from IISc has been proving their competence in the the iGEM competition for the last two years - with a bronze medal in 2016 and a gold and top 6 hardware nomination in 2017. Our achievements last year were covered in newspapers and by DBT-Infis . This year, we are aiming even further, the best therapeutics project award.

The team itself is composed of more than 20 undergraduates from the second and third year of IISc's Bachelor of Science (Research) program. We are also fortunate to have two extremely capable Professors from IISc, Dr. Sandeep Eshwarappa and Dr. Umesh Varshney as our PIs.


Why crowdfunding?

We believe that both funding and public outreach are very important for a project that aims to deal with problems that affect the general public. As a student funded endeavor, we start with limited resources. However, crowdfunding would allow us to raise the money needed to successfully complete the project and participate in the competition, representing IISc and India in the process. After careful consideration of all expenses, we expect the complete budget of our project and participation to be around ₹18,00,000 out of which, we aim to raise around ₹5,00,000 through this platform. Your contribution would be really appreciated not just for it's monetary value, but also for the encouragement it gives us to perform to the best of our abilities.

Corporate sponsorship

For corporate sponsorship please refer to our sponsorship packet and contact us.

Transfer funds directly to the bank account of this fundraiser:

Account Number : 6999413500057924 Account Name : IISc Bangalore iGEM Team Account Type : Current Account IFSC Code : YESB0CMSNOC

Note: Only INR transfers are allowed.
Once you have made the transfer, please visit https://www.ketto.org/contribute/payments.php to receive payment acknowledgement.
  • Phages in action!

    by IISc Bangalore iGEM Team on June, 06 2018

    #2

     

    We just tried our freshly opened T4 bacteriophage sample with E. coli. Here's a picture of how they affected growth over an hour.

    As phage concentration increases to the right, you can see that the turbidity (which is directly correlated with bacterial growth) is decreasing.



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  • We've begun characterizing mCherry

    by IISc Bangalore iGEM Team on May, 28 2018

    #1

     

    Latest updates from the lab

    We've begun isolating and characterizing our first protein for this season. This is a fluorescent protein called mCherry that glows red when excited. We are improving it to prevent truncation and improve yields. This will allow future researchers to create fusion proteins that can be used for variety of diagnostic and analytical purposes.





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