This week we had a nice summary of immunotherapy by Dr Robert, of which included exciting class discussions that really got me thinking deeper. Much more research has to be done to better understand the immune system, especially because of the possible adverse events that may occur to each individual. At the same time, as much as I think that the idea of a universal CAR-T cell is ideal, I think that there is a chance the immune system may still consider the CAR-T cells as foreign and we are unsure of the effects of knocking out the endogenous T-cell receptor.
As for the future of immunotherapy, there is definitely a large market potential given that it could possibly the least immunogenic and more sustainable if it comes from the patient’s own immune cells. Unfortunately, I think that its application may be limited to single antigen associated diseases or tumour. We would require a better understanding of the available antigens on specific tumour to avoid any off-target effects and that’s where the biomarker libraries will play an important role.
Right now there is a huge gap in the patient information that we currently have about different kinds of diseases and cancers, so there has to be a continual effort to improve the database of real world data. I believe with a more comprehensive understanding of the disease population, we can more accurately carry out high throughput screenings to choose the right target antigens for our ideal CART cells! No wonder data solutions companies like IQVIA, are so important to clinical trials and therapeutics discovery today.
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This week we heard each other’s presentations for the various CRISPR applications and I was most interested in the one presented by Sophia, whereby the paper investigated the use of hairpin secondary structures to improve accuracy. I feel like there would be a lot of potential if they are able to show more accurate evidence of its effectiveness because forming the hairpin structure itself appears quite simple and straightforward. However, being based on mathematical modelling, I had a tinge of doubt towards the accuracy of the results, more so when there were no previous studies or reasons sited for choosing their modelling software used. From this it made me question how easy it is for us to take for granted certain methodology, especially when it is either well-established or commonly used.
Personally, I thought it would be easier to analyse a short paper, but I was proven wrong. My own paper was theoretical in nature so, in terms of methodology and materials, I really struggled to find points to critique. But at the same time, the short article made me appreciate every line that was written, after having combed through each line over and over again. While critiquing the paper, I kept wondering, “Why didn’t they include this (or that)?”, and that is when I realised how important it is to accurately communicate information in a succinct manner. There are certain things that seem important but may not be relevant to the current proposition. The author has to re-evaluate the direction and focus of the paper and ascertain if the content is in line with the message to be conveyed.
I always look forward to our field trips, so I would say that the highlight for this week would be the trip to NovogeneAIT. Before the trip, I had been to Biopolis before and I knew it to be a hub for government agencies and other government-supported research companies. From what Robson had shared during the tutorial, I had the impression that NovogeneAIT was a very big company (given that they had multiple sequencing centres around the world. I’m not sure if I was mistaken but I think he was referring to the sequencing centres of Novogene, right? NovogeneAIT being the joint venture only here in Singapore. In any case, this made me expect a much larger space, so I was very surprised when they gave us a tour of a much smaller area. Nevertheless, I think that this still impresses me because they are able to process a large number of genome samples even with this small space and equipment. It really speaks for how advanced the processing of the HiSeq and NextSeq they are using is, that these few machines alone can produce so many libraries.
On that note, it really interested me when they were talking about the eventual goal to be able to sequence a full human genome for just $100. In a matter of a few years, the price has gone down to just around a thousand dollars compared to how expensive it was before. That means that one day, sequencing will become so readily accessible at an affordable price, we might be able to advance research at an exponentially fast rate as well since genome sequencing is being applied in many scientific areas. On the other hand, it also implies the business race of manufacturing companies to design faster and more advanced processors to be able to handle even more data at a cheaper cost. Seeing the sequencing machines reminded me of the development of computers from really huge machines that take up an entire room to the laptops and iPads that we see today. I look forward to the day we will be able to have a table-top sequencer that can process as many samples as the latest model of NovaSeq today.
One of the confusing things for me was the fact that they still relied on physical servers, although they are looking at exploring cloud servers and cloud processing. One of the biggest limitations is that they have to clear the servers of old data after 45 days, and only the processed data is being backed up into their cloud server. What if a client wanted to retrieve old data that was past 45 days? Or what if they wanted the raw data for some reason? Data storage is a big issue for a company like NovogeneAIT that has to handle terabytes of data every day. I think that data management is really important not just for big companies but even on an individual level. Keeping things organised and backed up properly makes it easier if you need to pass on the data to someone else.
This week we had a more in-depth look at the CRISPR-Cas system for the lecture. I think that it is very exciting when you realise that we are still at the tip of the iceberg when it comes to understanding the role and functions of Cas proteins in bacteria. And yet we have already discovered Cas proteins that are able to not just produce a double-stranded break but produce a single-stranded nick and even sticky ends. Repeatedly, however, seems to be that the real bottleneck of this technology is managing the offsite targeting effects. This still leaves room for error and with regards to clinical therapeutics, this is definitely something that you would want to eliminate as much as possible. We are however in a time when CRISPR-Cas system gene therapy is likely to see way more applications, as scientists continue to understand the functions and possibly uncover more immunological defence systems in bacteria that may help us too. The assigned readings (and their diagrams) really helped me to understand the mechanism of the different Cas proteins because initially, it was difficult to conceptualise. And the lecture helped to consolidate my understanding by reiterating what I had read beforehand.
I must add that the guest tutorial by Novogene AIT was a good addition to the week as it fed my interest in the business aspect of biotechnology. It must be quite hard to “stay ahead of the competition” all the time and is probably not as simple as the speaker had made it be. Understandably there are probably some marketing strategies he is unable to reveal, even though I wanted to know how exactly do they have intel about the latest software, technology etc. Trend analysis is also something that interests me, so I was glad to hear about how they work towards trying to predict the needs of their clients beyond what they request from them, showing them that the company is able to provide more services (and at the same time making more profit!). The idea of master contracts is also pretty strategic, instead of just targeting individual labs. With Singapore being very small, however, I can see why geographic segregation is also necessary. This idea of a concerted effort really pays off, not just in business but in everyday life. It is not efficient to divide your energy in too many places. As a service provider company, working closely with government agencies/authorities is probably a good move too. In Singapore where the government nowadays concentrates its resources on a lot of data-driven projects, such contracts provide a lot of stability and reputability. Lastly, the speaker’s comment on being a service provider in today’s economy really struck out to me. Being someone who is currently thinking about having my own business one day, it was really relevant advice. With today’s sharing economy, being a service provider is very advantageous and this business model has a lot of potential given the right service in demand!
I really enjoyed the field trip to SCIEX this week. I think that it is interesting to see how companies optimise their operations and also as a biotech company, how they continue to innovate and improve in an iterative fashion. They take into account not only customer feedback but even things like walking distance to optimise associate work efficiency.
As for the science technology, I think that its great that they are looking at forecasting the trends for mass spec analysis instead of just waiting on their customer demands. Having the best of both worlds in the QTRAP system is great for the future when we might be looking to analysing greater amounts in a shorter period of time, we will need to rely more on qualitative screening.
For lecture and reading, I enjoyed the review papers assigned to us. Gave me a comprehensive understanding of the mechanics of CRISPR/Cas9 system as well as the future modifications that can be done to it. Prof Liou did a good job in reiterating the reading material again, as well as the difference and advantages between RNAi and CRISPR. I think that RNAi has a lot of potential but it’s right to say that there is a lot of difficulty in getting it approved due to the off-target effects. Patisiran is the first RNAi approved as a therapeutic, so I think that there is way more that can be worked on this area.