The PokéCommunity Forums

The PokéCommunity Forums (https://www.pokecommunity.com/index.php)
-   Internet & Technology (https://www.pokecommunity.com/forumdisplay.php?f=57)
-   -   Event I am a cancer research scientist - AMA! (https://www.pokecommunity.com/showthread.php?t=370478)

Nihilego June 11th, 2016 5:35 AM

I am a cancer research scientist - AMA!
 
Hi PC!


So some of you who know me might already know that I'm a (currently training) biologial scientist. Specifically, my interests are in molecular and cellular biology and my current research is on cell communication in cancer metastasis. Soon, I will be leaving my current lab and moving to another where my work will predominantly be on cell membrane trafficking.

Since a number of people have been talking about AMAs in this section and since it'd be cool for us to have people who work in science talking about what they do, I discussed this with Team Fail and Tsutarja and we thought it'd be a good idea.

In this thread, ask me:
• About the general biology and biochemistry of cells and cell communication;
• About cancer biology - what it is, how it develops, how we treat it, and why it's so difficult to cure;
• About my work and the rationale behind it;
• About my day-to-day job and what I'm actually doing in the lab;
• About science as a career and (unfortunately) as a business;
• Anything else!

Please don't ask me:
• About my present results - these are unpublished and are therefore confidential;
• Questions about your own health which should be directed to a medical doctor;
• Anything about trees.


Go!

gimmepie June 11th, 2016 6:37 AM

What would you say are the biggest challenges facing workers in your industry? What, if anything, is being done to remedy these problems?

Xertified June 11th, 2016 7:21 AM

How do you treat cancer? How? And why it is that dangerous?

Margot June 11th, 2016 7:28 AM

How many people work with you on the research? Does your lab have multiple research projects going on at once, or do you all work on the same one?

I find this all very interesting & think these threads are a great idea! Especially for those of us who don't work in a science field and like to learn more about it :)

Brolaire June 11th, 2016 7:44 AM

What brought you into the field? Did you have an inspirational moment or was it more of a continuation of things you worked on in school?

Nihilego June 11th, 2016 8:14 AM

Brolaire, I saw your post after I finished writing this one so I'll reply to it in my next post!

Quote:

Originally Posted by gimmepie (Post 9281269)
What would you say are the biggest challenges facing workers in your industry? What, if anything, is being done to remedy these problems?

I'd say the biggest issue that impacts everyone, no matter what their level or standing as a researcher, is funding (or the lack thereof). Most principal investigators (PIs) agree that getting funding is one of the most daunting, time-consuming and demoralising parts of research. You have to send off loads of applications and, from the ones you hear back on, perhaps only 10% of the responses are going to be at all positive. I figure this is for a number of reasons; lots of countries simply don't have the money to invest into research (or don't want to invest it), meaning that lots of the applications have to go to third parties or charities - who have very limited money themselves and want to fund only the best-written projects with highly-qualified investigators who have access to a lot of modern, high-end equipment.


This is not only a problem for the PIs because it's difficult to get money to do the work they want to do, but it's hard for the lab workers too; if you've got no funded project you've essentially got no job and no security. PhD students won't be able to get places at all if they don't have a project which has been allocated funding, meaning that applicants for PhDs are often left hanging until the last minute to find out if they will have a place or not. When you don't have funding, it makes problems for everybody and that's unfortunately a very common situation to be in.


In the cancer field the situation's a little better because "curing" cancer is of enormous public interest, but for rarer or less severe diseases the funding often simply isn't there. If you're not researching diseases at all then that's a whole other layer of difficulty and restricted money that you've got to overcome. Really, it's not pretty all-round, haha.


In terms of what's being done to help the situation, it's not entirely in our hands; it's up to funding agencies and governmental bodies to realise the importance of funding for research. A lot of effort on our part, though, is going into raising public awareness of our work and showing them the importance of it. Lots of people aren't aware, for example, that it's not the medical doctors who are working on finding cures for diseases - it's us. Science is an undeniably complex field which lots of people shy away from, but the issue is that this translates to a lack of public interest which ultimately results in our work being devalued and being considered "lesser" in the public eye. And, as I said earlier, no interest = no funding. So engaging the public more in science and explaining to them why it's important and why we do what we do will hopefully result in more money coming in via charities and government bodies.

Quote:

Originally Posted by Omega (Post 9281320)
How do you treat cancer? How? And why it is that dangerous?

So at the most basic level, cancer occurs when general (but critical) cellular processes fail. Things like loss of control of cell division, surviving apoptosis (which is the scientific term for cell "suicide" - when defective cells kill themselves), and other basic factors lead to cells which divide uncontrollably and in areas which they shouldn't be dividing in. It's these processes which traditional chemotherapeutic drugs target - for example, if you give a drug which stops cell division to a dividing cancer cell, the cell usually dies.

The problem, though, is that all of the processes dysregulated in cancer are also present and functional in normal, healthy cells. With traditional treatment methods, you can't selectively kill cancer cells whilst leaving normal cells alone. If you admininister a drug which kills dividing cancer cells, you also end up killing dividing normal cells. Forcing apoptosis in cancer cells forces it in all cells. So while these drugs can work in killing cancers, the side-effects are pretty severe because they're able to target theoretically any cell in the body which makes use of the mechanism that the drug targets.

Another way to treat cancer is radiotherapy - which works by inducing massive numbers of mutations in the DNA of cells so that they're unable to stay alive. This is pretty good for solid tumours which are difficult to operate on or to make sure that areas which have been operated on are completely free of remaining cancer cells, but has the nasty side-effect of also killing normal cells unspecifically if they're too close to the area being radiated. Additionally, cells which survive radiotherapy actually have a small chance of becoming cancerous themselves (bear in mind that cancer is a disease induced by genetic mutations), so it's really not ideal.

Surgery is the last common method of cancer treatment, and it's actually pretty good against early-stage solid tumours. The danger arises when the tumour is in a sensitive location (such as the brain or the lung), or when it's a quite advanced tumour; tiny surgical mistakes can introduce cancer cells into the bloodstream which gives a massive risk of metastasis. Still, it's good for very early-stage cancers and often makes long-term chemo/radio unessecary.

The best cancer therapies - some of which are being worked quite intensively on right now - will involve either the delivery of drugs specifically to the site of the tumour or will involve exploiting the features of cancer cells which are absent in normal cells, such as mutated versions of proteins. A big example of this which is becoming popular right now is the concept of a "vaccine" against cancer, where the immune system can be primed against mutant proteins found often in cancer. But for now, the therapies which we've got are mostly double-edged, unfortunately.

Quote:

Originally Posted by Kyoko (Post 9281331)
How many people work with you on the research? Does your lab have multiple research projects going on at once, or do you all work on the same one?

On my project, it's mostly just me and two others right now. We're pretty understaffed on this one, haha, although we're getting some more people before I leave this lab. The lab is about 15-20 people, which is quite a lot relatively speaking, so we have many projects going on together. Off the top of my head I think we have 6 or 7, and some others which are either waiting for funding or have just recently been funded and are waiting to get going, along with some other collaborations we have with other labs. I'm working one of three cancer projects right now, while the other projects are focussed on other diseases. Funnily enough the lab's main interest is in bone diseases; the specific aspect of cancer that I work on is metastasis to the bone, which is what ties me into this lab in the first place.

Karma Police June 11th, 2016 8:36 AM

What are the biggest misconceptions people have about 1) your job 2) cancer, as a disease?

Is a cure for cancer even possible?

Nah June 11th, 2016 9:14 AM

Where exactly do you see yourself in your field in like, 10 years or something? Give us your thoughts on the "science as a business" bit?

And:
Quote:

Please don't ask me:
• Anything about trees.
......why can't we ask you anything about trees (why would anyone even think to ask that anyway?)?

Tsutarja June 11th, 2016 2:17 PM

So glad to see this up! :]

I'm not sure if you knew about this, but my mother passed away on New Year's Day this year after a near year-long battle with multiple myeloma, having been initially diagnosed at Stage 3. Do you have any experience in studying, researching, and/or working with this disease?

Klippy June 11th, 2016 3:04 PM

Here's something a bit different.

Cancer is such a globally-affecting disease and one that is both connected through all of us (cancer donations and charities, cancer research, celebrities getting it, almost everyone knowing someone or of someone who has it, etc.) to how society exists, but in a world where cancer is completely curable and treatable like taking a vitamin or a flu shot to prevent it altogether, how do you feel society would change?

More simply: what if cancer was easily curable?

KetsuekiR June 11th, 2016 10:09 PM

What would you say is the best and worst parts of working as a cancer research scientist (besides the possibility of curing cancer)?

bobandbill June 12th, 2016 12:41 AM

What are other diseases that you feel should have as much of a spotlight on as cancer?

Also, what are your typical day-to-day duties/tasks? Even in the same broad field scientists do different sorts of things to each other.

Nihilego June 12th, 2016 4:08 AM

Phew, that second answer took a while. I'll reply to the next four posts (Tsutarja, Klippy, KetsuekiR, bobandbill) when I've got time to.

Quote:

Originally Posted by Brolaire (Post 9281354)
What brought you into the field? Did you have an inspirational moment or was it more of a continuation of things you worked on in school?

A bit of both, really. So I dunno if you're familiar with how the UK education system works but in case you (or anyone else here) aren't, we study a broad range of subjects up until we're 16-or-so and then, if we choose to continue with education, we go on to "specialise" in 3 or 4 subjects before proceeding to university where we focus entirely on only one subject (no "majors" here).

So up until this 16-year-old point I was never actually that into science. I mean, yes - I did enjoy it and I was pretty good at it - but it wasn't my 'thing' if you know what I mean. That was more about music and art and sport, which is what I was for sure known for at the time. However, as much as I enjoyed these, I never really wanted to try to make them into a long-term career (nor did I think it'd be feasible to do so - not that science is much better as it turns out, haha). So I found science quite interesting and knew I was generally good at it so I went with that.

It wasn't until later that I figured out that biology had always been the obvious choice - whenever I learned anything to do with how biological things work I wanted more and more and more and more detail until I knew every single molecule behind the process which I was looking at. This is basically the curiosity which drives my whole field, so I'm really glad I decided to follow through with it.

Quote:

Originally Posted by Karma Police (Post 9281412)
What are the biggest misconceptions people have about 1) your job

One of the biggest ones is the idea that we're all medical doctors. As I mentioned earlier, lots of people think that it's the medical doctors who are doing the research, and I guess it kinda makes sense; they're the ones that people see giving paitents drugs and making them better. But in reality, medicine and medical science are very different things handled by discreet groups of people. It's very rare in my field for someone to have a degree in medicine and much rarer for them to be working in both fields. While we do work alongside doctors and on rare occasion paitents for things like the collection of tissue or blood samples, we're very different people. It's a bit annoying really because you hear stuff all the time like "doctors have discovered this new cancer treatment" (or whatever) and it's not actually the medical doctors who've done it - it's the scientific ones, but the credit often goes to MDs anyway.

There are also a lot of misconceptions about animals and animal experimentation - why we need animals (mostly on this point), what we do with them and how we treat them. But that's a whoooooole other topic which I'll go into more if anyone wants me to.

Quote:

2) cancer, as a disease?
Probably the biggest one is that all cancers of one type are the same, which leads people to believe that treatments should be standard between different paitents. One paitent's breast cancer, for example, won't be the same as that of another. Cancer arises as a result of mutations in proteins, but the possible combinations of mutations are innumerable. While common trends can be seen in mutated proteins (for example, mutations in a gene called p53 - coding for a protein which regulates steps of cell division, DNA repair and cell death, among other things - are reported to be present in anything from 10% to 90% of cancers, depending on cancer type and stage), it's unlikely that the exact combination of mutations causing the disease is going to be the same in two paitents. It takes several mutations to cause cancer, not just one or two, and there are a great number of genes known to contribute to and to cause cancer. This is why there's no one "gold standard" therapy for cancer, and why different paitents can have such different treatment regimes and outcomes. In addition to this point, not all of the cells in a single tumour are the same; a developed tumour can have many subpopulations of cells which respond to different drugs. This is why one treatment might be able to kill 95% of a tumour but a resistance shows up at the last minute, thus calling for the use of another drug.

Quote:

Is a cure for cancer even possible?
Argh, this is a tough question to answer, haha. Right now there's no general consensus on if it's possible to cure or not and it's a really hotly-debated topic but, unfortunately, I think the "no" side of the argument is starting to win. Certainly, it's the side that I'm on.

All of this is just my opinion of course, but I don't think that we're ever going to find a definitive "cure" for cancer - partly because of what I said above about cancer being highly heterogenous, but moreover for another reason: cancer should be considered as an evolutionary disease. In evolution, members of the same species evolve certain traits which allow some individuals to outcompete others and to have better reproductive success, and this is also happening in cancer. Cells in a tumour more capable of destroying matrix surrounding the tumour to make more space to grow in, for example, are likely to survive better than those which can't. Cells which can detatch from the primary tumour and enter into the bloodstream are more likely to form metastases, while the others will get left behind. It's essentially cancer's own version of extremely rapid and aggressive natural selection.

More importantly when we're talking about a cure, cells which can resist a drug treatment will overtake cells which cannot. This means that drug treatment can actually select more fit cancer cells to propigate future tumour growth; you can treat a paitent with a drug which seems to be working only to later find that cells start showing up which resist the drug. In fact, I watched a really interesting presentation recently where a group treated late-stage colorectal (iirc) cancer paitents with a drug which targeted a mutated version of a protein called EGFR (whose mutants are common in cancer, and are important in signalling for cell division) and observed that most of the cancer died, until three months later... when no fewer than six individual further mutations of EGFR showed up which highly specifically resisted the drug's mechanism of action. This really highlights to me just how able to resist treatment cancer can be and, no matter how well-targeted our drugs are, aggressive cancers will find ways around them.

There's also another phenomenon called tumour dormancy, which is a big problem for "curing" cancer; following treatment, a cancer can visibly seem to be completely gone, but there could very well be "dormant" cancer cells left over - these are cells which have stopped dividing and invading like normal cancer cells, but which still harbour the basic cancer characteristics. The big problem here is that, when using drugs which target features of active cancer cells, these are very capable of slipping by unnoticed. A cell that's not dividing won't be harmed by a drug targeting cell division, for example. These cells can remain dormant for years, coming back as a secondary cancer anything up to decades following the "cure" of the original tumour. So it's very difficult to say usually whether or not a paitent's cancer truly has been beaten, or if it's just the active cells that have been removed.

So the long and the short of it is that, no, I do not believe that we will find a definitive "cure" for cancer. It has too great a variation in possible mutations and it's too capable of evolving in real-time to find its way around drugs that we throw at it. When it seems like cancers are gone, there could well be dormant cancer cells still alive which can cause relapses later in life.

It's not all this bleak, though; everything I've said here is characteristic of quite advanced cancers which have probably already reached the point where they've got virtually no control over their mutation rates and are able to spread easily. Early, more simple tumours are certainly very treatable, and I do believe that we'll get to the point where we're able to cure any cancer featuring a single solid tumour which was detected at an early stage. In fact, we're almost at that point now; 90% of cancer-related deaths come from cancers which are highly advanced (or, to be more specific, post-metastatic: it's the metastasis, not the primary tumour, which usually causes deaths), with only a minority of deaths being caused from non-metastatic early-stage tumours. It's just about finding it early and getting rid of it quickly. This, combined with preventative tactics (for example, blocking metastasis - which is a big part of my present work), will hopefully stop cancers being able to progress to such late stages, acting as a sort of "proxy" cure. We're a way off that but we'll get there, I hope.

Quote:

Originally Posted by Nah (Post 9281452)
Where exactly do you see yourself in your field in like, 10 years or something?

Really hard to say. I don't actually think, at least in the next few years, that I'll be staying in cancer (or rather, my work may continue to involve cancer but it won't be my main focus). There's a really exciting new field in cell biology which we have incorporated tightly into our work which I want to go into. There's a type of molecule called an extracellular vesicle (EV). They're these little sorts of "bags" of biological material released by cells to other cells, which can deliver pretty much anything you find in a cell - proteins, RNAs, etc. EVs are becoming really interesting because they can specifically target cells in tissues and deliver their content to change the behaviour of these cells. There is no other signalling mechanism which can deliver specific molecules to target tissues anywhere in the entire body. Furthermore, EVs certainly have roles in many diseases including cancer, so they're becoming recognised as very interesting and important. I want to get much more involved with them because it's a new concept but one which I think will prove to be very important in the near-future, and now is a great time for me to jump into it.

Also, at least from what I've seen, if you try to go into cancer long-term too early you probably won't get far - it's such a hot topic and there's so much competition that there's no way you can really make yourself stand out. In my opinion, you should become proficient in some other field and then apply it to cancer if you really want to get somewhere, which is maybe what I'll do later down the line. I dunno. It's a hard thing to say since in science 10 years is a really long time and your research interests and ambitions can change dramatically over that time. But yeah, this is the direction I'm headed in now; go into working on EVs, with or without cancer, and see where it takes me.

Quote:

Give us your thoughts on the "science as a business" bit?
I feel like there's a fairly strong element in science of "but does it make me money?". Similar to what I said earlier about the funding, people are much more interested in the big money. Lots of people defect to pharmeceutical companies or to research fields which they're not interested in, but which promise greater pay, for this reason. It's a shame since I think that if everyone did the science they enjoy doing as opposed to what'd make them money, we'd put out some much better research in more diverse fields, but eh. What can you expect, I guess.

There's also a lot of people trying to climb over each other, particularly in cancer. When someone makes an important discovery, you get 10 people jumping on them trying to get authorships on their work or even trying to take the credit for it when they, realistically, haven't done that much. There's a lot of drama over who gets published on whose papers and in what order and etc. and it's all a load of bullshit, honestly. Science does, unfortunately, often lack a lot of integrity when it comes to fairly crediting people for their work, with more "senior" people often taking the credit for the work of people "below" them based on seniority alone - despite having done nothing for the work themselves. It happens way too often and it's one of the few massively unfair things that's genuinely made me think about leaving science before. Even now just typing this I'm getting pretty irritated over it, so I'm gonna stop, haha.

Quote:

......why can't we ask you anything about trees (why would anyone even think to ask that anyway?)?
Aha, it's a sort of joke among biologists that all we want to do is sit around and hug trees all day.

Her June 12th, 2016 4:30 AM

Quote:

Originally Posted by Razor Leaf (Post 9282510)
There are also a lot of misconceptions about animals and animal experimentation - why we need animals (mostly on this point), what we do with them and how we treat them. But that's a whoooooole other topic which I'll go into more if anyone wants me to.

Sure, go into this whenever you happen to have time.

Spherical Ice June 12th, 2016 8:30 AM

How much of an impact do cancer research charities actually have on your field, if at all? How much of the money do you (the researchers in general) actually see?

Return June 12th, 2016 9:01 AM

How Cancer develops? Is Cancer can be prevented at all?

Nihilego June 12th, 2016 10:45 AM

Ahaha, these questions are coming in quickly and they're pretty good and I want to give them all the time that they deserve - so apologies for not answering them as soon as they appear. If your questions aren't answered in my post then assume that I'll do them in a future one instead.

Quote:

Originally Posted by Tsutarja (Post 9281806)
I'm not sure if you knew about this, but my mother passed away on New Year's Day this year after a near year-long battle with multiple myeloma, having been initially diagnosed at Stage 3. Do you have any experience in studying, researching, and/or working with this disease?

Yeah, I remember that. I don't know if I said it at the time but I'm sorry for your loss. I know that multiple myeloma is osteolytic (bone-degrading), and I know the molecular mechanisms behind that, but otherwise I can't say that I've studied it much. Our group is very interested in osteolytic cancers since osteolysis is a major factor in bone metastasis, and blocking osteolysis could be one way to stop that. Our focus is more on breast carcinoma, though, so I really can't say much more than that.

Quote:

Originally Posted by Klippy (Post 9281850)
Cancer is such a globally-affecting disease and one that is both connected through all of us (cancer donations and charities, cancer research, celebrities getting it, almost everyone knowing someone or of someone who has it, etc.) to how society exists, but in a world where cancer is completely curable and treatable like taking a vitamin or a flu shot to prevent it altogether, how do you feel society would change?

More simply: what if cancer was easily curable?

Ahaha, good question. The long and the short of in my opinion is that I'd be out of a job people would die in another way, and it'd probably be cardiovascular disease (CVD). That's not to say that trying to cure cancer is pointless since obviously it's a really nasty disease that can impact everybody and causes pretty severe losses to quality of life, but lots of cancer deaths actually happen shortly before a peak in CVD-related deaths. For this reason I'm inclined to think that, if cancer were to be completely obliterated, CVD would just move even further into first place as the leading cause of death. I figure life expectancy would probably increase since iirc people tend to die of cancer before CVD, but not by all that much. That said, if we were to eliminate cancer and then focus all of the cancer research efforts into CVD, we'd probably start seeing some serious increases in life quality and expectancy, so that's a big knock-on effect I could see coming out of a hypothetical easy cure for cancer.

Interestingly, lots of advances in understanding in cell biology have been due to cancer. Cancer gives us a model whereby we have cells with dysregulated processes as a result of mutations in particular proteins - and these are cues for us to study those proteins and understand how they work and ultimately, how they link into cell behaviour. If there was no more cancer (and therefore, no more cancer research) this'd be stunted. I can imagine it being much tougher to get basic research funded because cancer is the driving force behind a lot of projects (i.e., "this protein has been identified to cause cancer and we want to study it more to understand why and to progress towards a cure"), so in that way an easy cure for cancer could actually be harmful to science - although this is all just speculation on my part. I'm certainly not saying that I'd rather cancer not be cured here, mind.

Quote:

Originally Posted by KetsuekiR (Post 9282244)
What would you say is the best and worst parts of working as a cancer research scientist (besides the possibility of curing cancer)?

I'd say that the best and worst parts of working as a cancer scientist can extend to pretty much any field of research (at least, in biological sciences). You get to spend all day every day doing work which has never been done before on something you're deeply interested in. You get to talk about your findings with your lab colleagues and other people and work with them to decide how to move forward. You get to have genuinely interesting conversations with people who want to know more about what you do, just like the conversations we're having right now. If you like what you do then research work has gotta be some of the best work in the world. That, and there's nothing like the feeling you get when you've got a good result which you know is going to be important for you somewhere down the line; the trails of speculation and brainstorming ideas and etc. that it sets you on are amazing. And, ultimately, there's nothing as satisfying as seeing your name on your work which you publish or present somewhere. If you enjoy what you do, you're happy to trudge through all the education you need and the technical issues and all that because you want to get to the end of it. It's awesome.

The bad, though, is pretty bad. The thing that probably bothers me most is what I wrote in my reply to Nah - about how business-like it can all be and how people try to climb over each others' work all the time. I do spend a good amount of my time just bluntly thinking "please just fuck off for a bit and let me do my work" and I know that many other scientists do too, haha. The work itself is very difficult and is probably not well-enough paid (this could go in my earlier "misconceptions" list, actually - we really aren't as well-paid as we're made out to be), but that's not such a big deterrent if as I say you're doing the work for the joy of it. The big problems are for sure the business aspects of science, for me anyway. Animal work is pretty draining too sometimes, and maybe I'll touch on that some more in my reply to Harley Quinn later on (unless anyone has more specific questions).

Quote:

Originally Posted by bobandbill (Post 9282379)
What are other diseases that you feel should have as much of a spotlight on as cancer?

More molecular studies into mental health issues (particularly the more severe and long-term ones such as schizophrenia, bipolar disorder, etc) would be really awesome. Most of the research in mental health revolves around paitents' behaviour, what causes issues, types of therapy, etc. but for the most part there aren't molecular diagnostics available for mental health issues and their molecular bases aren't well-known. If we worked more on this sort of thing we'd be able to identify dysregulated productions of particular molecules or over/underactivation of certain pathways. The sort of "holy grail" of mental health issues that I've got in mind is one where, not unlike what we have in cancer, we can make precise diagnoses for people right down to the individual processes which aren't working properly and be able to target them specifically with medication. I'm not saying for a minute that mental health issues can't be resolved without medication, since for sure talking therapies and etc. do work for some people with some conditions, but in cases where medication is called for the current medication that we have is very much "one size fits all" and often involves trying several types of medication out before one that works is found (which, again, supports the idea that it's not the same molecular processes causing mental health issues for everybody). A better understanding of exactly what causes mental health issues and medications which can target these things exactly would be amazing.

Another, more specific disease, is diabetes. Although the therapies which we have for Type 1 diabetes are reasonably effective and safe, they aren't completely ideal and furthermore there is no gold standard consensus medical treatment for Type 2 diabetes. Diabetes is perhaps the most common disease which impacts almost every single body system - almost the entire body is reliant on proper glucose homeostasis which is badly controlled in diabetes. The result is that, if the diabetic person for some reason is unable to access treatment or whatever, you end up with massive systemic issues that can cause an extremely broad range of problems. The impact that diabetes can have on the body is pretty underestimated and poorly-appreciated imo, even often by diabetics themselves who are told that it's a straightforward disease. Glucose metabolism and homeostasis is one of the most conserved, intricately regulated and all-round important processes in the body and in diabetes it's messed up - yet, in my view, diabetes doesn't recieve the attention or the research that it deserves. Particularly given that Type 2 diabetes is on the rise, more has to be done to research it and find more efficacious ways to combat it. There are a great number of ways to treat both conditions at present, but neither of them have been fully "cured" and the sheer number of ways that there are to treat the disease is an indicator of how hit-and-miss they can be.

Finally, I guess you could give osteoporosis a mention. I feel like osteoporosis is kinda allowed to slip by because it's not a very severe disease and it is extremely common, but it can actually be quite damaging to quality of life and near-immobilising in severe cases. Furthermore, there are a lot of easily available treatments for osteoporosis which can both prevent its onset and alleviate some symptoms after its onset which people simply don't know about. I think this could use a bit more attention in the public eye since it doesn't have to be "just one of those old-age things" and is actually quite manageable. It's a fairly straightforward and well-understood disease too, so really it's just down to getting the treatments out there to the people who need them.

Dunno if I'd say that any of these warrant "as much" of a spotlight as cancer does, but certainly, these warrant far more attention - as do hundreds of other diseases. Cancer is very much stealing the show with medical research and it's a bit of a pain for everyone with a problem that isn't cancer, haha. I could go ahead and name another fifty diseases which need more attention but I'll stop there; those are three things which in my mind could do with a bit more attention paid to them.

Quote:

Also, what are your typical day-to-day duties/tasks? Even in the same broad field scientists do different sorts of things to each other.
Depends a lot on what sort of experiments I'm doing on the day in question, but there are a number of common things which I'm doing every day - specifically, cell culture (which is central to all of our work in the lab) and EV preparation (see above). If we have no cells we can't do any experiments, and we're able to get only extremely tiny amounts of EVs with a single isolation so we need to do a lot of them. We also have a lot of mice to take care of, and we check them, their health, and their breeding daily. Our lab is pretty large yet lacks any dedicated lab technicians, so we're all occasionally doing lab tech things (making stock solutions up, cleaning things, restocking equipment, etc.) to keep everything running smoothly. Then we have lots of regular meetings and presentations so there's ususally something "dry" to be getting on with. All of this is just background stuff that goes on in-between running experiments and actually getting results. In biology, there's usually a lot of waiting involved; many processes take hours or even days (such as cell growth), so we can be running several experiments simultaneously to make better use of time. All-in-all it's pretty busy, haha.

...I think that's what you were asking, anyway. If I didn't answer your question properly then just let me know.

Karma Police June 12th, 2016 2:56 PM

Why is it that certain types of lifestyle choices, such as smoking, increase the likelihood of getting cancer?

Adding onto my earlier cure question, would it be possible, in the future, to prevent cancer entirely? As in, be able to reduce the chances of these mutations occurring at all?

Thanks for the in depth answers by the way, they're really insightful.

Nihilego June 14th, 2016 1:08 PM

Sorry, been busy with work. Lots of new data to collect and organise right now - exciting times!

Quote:

Originally Posted by Harley Quinn (Post 9282520)
Sure, go into this whenever you happen to have time.

So I'll be quite broad here since I a) am not massively experienced in animal research and b) don't know which part of animal research you want me to focus on most.

I guess the most important thing in my mind which I'd like to communicate is why animals are so neccessary for all of us. When you want to publish a bit of research (particularly if it's medical research), one of the critical questions is "does your idea actually work in living creatures?". If you've come up with a pathway which you think is dysregulated in a disease or if you've come up with a drug which you think could cure a disease, but you've only been able to show these things in vitro (in the lab - dishes of cells, reaction tubes, etc), you've got a huge problem. It's not at all uncommon that in vitro something works but when you put it in vivo (in a living animal) it doesn't work for some reason - this could be due to the idea itself being wrong in live animals or due to unknown / unexpected factors in the animals interfering with the idea, among other possibilities. Particularly given that we're publishing work here which we hope to one day translate to human health, we absolutely must be able to show that what we're doing has a role in a living animal. The medical research community cannot work off of "findings" and "treatments" which only apply to cells in plates in incubators. If we're going to build on a finding, we have to know that this finding is relevant to a living creature, and it's the medical community's duty make sure that ideas for application in humans which have not been tested in vivo don't make it into disease-focussed journals.

Unfortunately, this does sometimes turn into a case of "we want to publish, so let's do things with animals until something happens and work backwards from there" which is a really bad mindset and one that I absolutely hate - animals should only be used when there is serious in vitro evidence to back the use up. This causes problems sometimes as I said before for some people who have done years of in vitro work only to find that when they go in vivo, nothing happens - but that's more often than not due to something which has been overlooked or which isn't properly explored yet and which, in the hands of the right researchers, could easily open up new routes of investigation. All in vivo data, including negative results, is extremely valuable and the animals which provide it are taken much more seriously than walking bags of cells. When an animal is sacrificed (and yes, that's legitimately term for it) at the end of an experiment, absolutely everything possible is collected from it - not just the tissues in question but all of the tissues, its weight, the weight of the tissues, the animal's fat distribution, tumours and other unexpected tissue structures, anything and everything which could be used later to provide data and to avoid having to re-do the experiments in further animals. Things like the animal's behaviour, sleeping, metabolic and mating habits may have been noted too if the animal is being used for any related studies. These are really goldmines of information and they aren't used lightly by good investigators.

So the next question which I guess arises is what can be done to reduce the use of animals or to substitute them for something else altogether. I hear a lot of people who suggest using tissues taken from animals (the advantage here being that a single animal can provide many tissues) or donated from human patients to emulate the real thing and to an extent, it's a good idea which lots of people make use of. We, for example, can use slices of bone from donor paitents on which we culture cells to test the impact that a particular treatment or condition has on the ability of cells to degrade that bone. These sorts of things are called ex vivo (i.e., "out of the living") techniques and they're extremely useful to test basic hypotheses in more complex systems that dishes of cells. Artificial tissues and organs are also becoming popular too - although there is scepticism around how "realistic" they are and they don't truly satisfy the idea of an ex vivo experiment. However, neither of these systems alone is enough to draw meaningful conclusions from; as I said before, they can test basic hypotheses (and, if the hypothesis is incorrect then they can postpone or fully prevent progression to in vivo experiments), but if the results from these experiments are positive then the experiment will still have to progress to in vivo. There's only so much that a single tissue can tell you, even if that tissue is your tissue of interest, and when you need to know what your condition does beyond a single tissue then you need an animal to do that in. You could ask, "why not use more tissues?", but it's extremely difficult (if not impossible) to properly mimic the communication between these tissues ex vivo without adding even more tissues to the equation, and eventually you just end up asking the question "why not just use an animal?".

Another important use is genetically modified animals. We can use animals to study the function of genes by methods such as disabling or overactivating that gene in animals - either systemwide or in specific tissues under certain conditions. This is possible (and far easier) in cells, too, but these methods do not give a systemwide overview of the gene's effects. For example, we could have some gene which we hypothesise inhibits the division of bone-forming cells (osteoblasts) in mice. We knock this gene out in mice and find that, yes, their osteoblasts divide more - but we might also see, for example, that mice which have lost this gene spontaneously develop lung cancer (or whatever). This tells us that this division-regulating gene which we thought functioned in bone may also have a role in the lung and, further to that, may be important for preventing cancer in the lung. This is a real wealth of information which we could never have obtained from a homogenous population of cells in culture, and it's not at all uncommon to see unexpected consequences such as this from modifying animal genetics.

The last thing worth touching on would probably be in silico modelling - using computers to predict what would happen in animals instead of using the actual, real thing. However, most scientists agree that we do not currently have the knowledge to reliably predict large-scale biological processes on computers. While a few specific pathways or processes have been successfully emulated by computers, and while computers are great for target prediction (see later), we would need a comprehensive understanding of every single interaction going on between every single molecule in mammals to have a true in silico model of a living animal, at which point we'd be pretty much done with cell biology anyway, haha. So although the theory is nice and although some fairly basic things are possible already in silico, the in vivo models are still needed to verify these results and we're a long way off being able to faithfully extend in silico results to humans. Computers are, however, extremely useful right now for predicting interactions - for example, guessing where protein might bind DNA based on the DNA's sequence and the protein's structure, or how two nucleic acids could interact. These are applications definitely useful, but we can't scale them up to entire animals or draw sound conclusions with regards to the functional consequences of these interactions yet.

This reply probably raises some more questions, so please do ask away.

Quote:

Originally Posted by Spherical Ice (Post 9282817)
How much of an impact do cancer research charities actually have on your field, if at all? How much of the money do you (the researchers in general) actually see?

In terms of how much impact the charities have on the field, it's absolutely massive - almost everything, in fact. Most of our funding comes directly from them; it's just that some fund more while others spend on themselves more (see below). Our own work would not be possible without funding from a cancer research charity in this country.

With regards to how much of their money we actually see - this is a really interesting question, but unfortunately I don't have experience with enough charities to say for sure - nor am I able to see which other projects charities are funding. The trend that I see in general is that the smaller the public interest in the topic that the charity works on is, the greater the proportion of its money put into research is - probably due to lacks of funding not leaving them much to spend on themselves after investing into the work that they promise to support. One of our major funding bodies, for example, specifically funds rare diseases including rare cancers and puts an enormous amount of their finances into actually getting science done whereas one of the major UK charities for widespread diseases (I can't remember which) was found to be putting in only a tiny portion of its money. So I'd say that it depends on the charity and the nature of the work being funded (or in the case of your specific question, which cancers are being funded) but I'm honestly not fully-equipped to answer this question.

Kanzler June 14th, 2016 1:46 PM

To what extent do you collaborate with medical doctors in your work? Do you have a physician-scientist PI or perhaps have close ties with another lab that's more applied in nature? How often does your lab communicate with medical practitioners?

Do you mind giving a bit more detail about the project you're working on? Like a mini-abstract or something.

Nihilego June 16th, 2016 1:39 PM

Just a quick update, I'm completely bogged down with work right now - loads of stuff has come up at once which I need to do so I'll get to these this weekend. Sorry that this hasn't gone as smoothly as I'd have liked it to have, haha.

Nihilego June 19th, 2016 6:41 AM

Quote:

Originally Posted by Karma Police (Post 9283149)
Why is it that certain types of lifestyle choices, such as smoking, increase the likelihood of getting cancer?

This is a big question really. The short answer is that it depends almost entirely on which lifestyle choice we're talking about. While, however, the exact mechanism by which different activities can increase the risk for cancer, they all share some common features - they can either directly modify DNA in some way, inhibit or damage DNA repair machinery in the cell, or decrease the replication accuracy of the DNA-duplicating enzyme DNA Polymerase (often as a byproduct of the first of these three processes - DNA Polymerase has only a very limited ability to accurately handle DNA which has been modified). So the long and the short of it is that it all revolves around some means of inducing errors in DNA, but as I say these mechanisms are quite diverse.

To quickly cover DNA's structure, in case you don't already know it, DNA is basically a long chain of individual sugars attached to groups called bases, named adenine, cytosine, thymine and guanine (or A, C, T and G). The individual order of the bases is what determines what DNA codes for, and it's therefore important that the order is maintained properly and that the bases are not modified.

To take your smoking example, as you probably know lots of chemicals in cigarette smoke are carcinogenic. Most of these chemicals, though, will have different mechanisms of action. A particularly well-known and highly carcinogenic one is called benzopyrene, which is a small, flat molecule made of cycles of carbon. It's a product not only of cigarette smoke but of pretty much any combustion process - burning coal, wood, etc. and on its own it's pretty much inert and safe. However, its metabolism in the cell converts it into another molecule which has an additional oxygen capable of reacting strongly with guanine, one of the four bases incorporated into DNA which I mentioned above. This binding distorts DNA's structure and induces replication errors, ultimately leading to an increase in mutations which can accumilate to cause cancer. This, taken together with the fact that cigarette smoke's tar buildup physically brings benzypyrene into close proximity of cells in the airways and in the lung, makes cigarette smoke a pretty effective delivery system for carcinogens (or, strictly speaking, procarcinogens - since benzypyrene is harmless before its metabolism). Additionally, in the lung, benzypyrene can diffuse into the bloodstream, explaining in part why smoking cigarettes increases cancer incidence in non-respiratory organs. This is just one of probably hundreds of carcinogens in cigarette smoke.

Another example you could give is the use of sunbeds, which use UV radiation to give you a tan. UV radiation is actually pretty high-energy and exerts enough of that energy on DNA to physically change its structure - more specifically, it causes dimerisation of bases in DNA. This means that two ajacent bases in DNA, assuming that these are the correct bases (or more specifically, cytosine and thymine), can join together not only as part of the main DNA backbone but directly to each other as well when influenced by the excess of energy provided by UV radiation. This is actually a fairly common form of mutagenesis since the sun itself radiates UV, and there are ways for DNA repair machinery to correct it - although interestingly, mammals including humans lack a truly specific mechanism to repair this sort of damage (and are therefore more susceptible to it), instead having to rely on more general repair mechanisms such as cutting away and re-synthesising entire regions of DNA containing photodimers. However, depending on the environment that the dimerisation has occured in, sometimes this cannot be repaired and in this case, DNA replication errors are almost certain to occur when DNA polymerase is unable to "read" the two joined-together bases. Indeed, this is a major driving force in melanoma development, which is tightly linked to excessive exposure to harsh sunlight and the use of sunbeds.

So tl;dr it's a pretty long story depending on which specific lifestyle choice and its respective mutagen you're looking at. Mutagens can be chemical like benzypyrene or physical like UV radiation, and there are loads of mechanisms behind them. The common theme, though, is that there is some process involved which messes with DNA or its maintenence and replication machinery, ultimately inducing mutations or increasing error rate, which leads to cancer.

Quote:

Adding onto my earlier cure question, would it be possible, in the future, to prevent cancer entirely? As in, be able to reduce the chances of these mutations occurring at all?
Ahaha, you're great at contentious questions. The general opinion is that prevention of cancer is far superior to cure, due to the difficulty of actually getting a "cure" and the side-effects that current treatments have. The problem, though, is the sheer abundance of ways in which mutations are induced, which raises the question - is truly trying to prevent cancer worthwhile? To completely eiminate UV-induced DNA damage, which as I explained is a massive cause of melanoma, for example, you'd have to stop going outside while the sun is up. This is not at all feasible and most people (i hope) would rather be able to go outside and take the risk on melanoma than spend their entire life shut indoors. To eliminate benzopyrene we'd have to not only all stop smoking (which would be a good thing, sure) but stop combusting things - including food. Cooked meat, particularly meat done on barbeques, contains pretty high amounts of benzopyrene. We'd also have to stop burning fuels in cars and fires. While this is all very nice for us and the environment, it isn't realistic given our current lifestyles or probably even desirable. There are loads of other very basic lifestyle things which induce cancer, and some of them are probably completely unavoidable. Exposure to heat over 37ºC, too, is a cancer risk factor; so say goodbye to hot showers.

So, yes, it's possible to reduce mutation rates but if it's feasible or desirable is another question, and the extent to which we could completely eliminate environmental cancer inducers is still a pretty tough question which I doubt we'll be answering any time soon.

I do, though, need to point out one other thing - not all mutations are environmental. In fact, lots of them are caused by errors in DNA Polymerase itself. It's important to consider that, throughout all of life's existence on earth, the driving force for evolution itself is mutation. The same thing that drives cancer. Change in species is induced by the selection of members who have mutations which give them an advantage over other members; be it more toxic venom, more intimidating markings, or more suitable anatomies for getting food (see: giraffes). So for the progression of species, an inherent ability to mutate is actually necessary. This means that DNA Polymerase, by design, is imperfect; its error rate is fairly low absolutely speaking, estimated in humans at ~1/108 errors per base replicated (and many of these errors are then repaired anyway), but when you consider how many cells you have with how many DNA strands are being replicated at once, this is actually quite a significant chance of error. Iirc human DNA Polymerase is generally considered more error-prone than most, too. The problem for humans is that we no longer have much selection pressure in the developed world, so this "error by design" is largely redundant and backfires quite heavily against us - furthermore, we can't naturally select for people with more stable DNA Polymerase because cancer is typically an old-age disease, and therefore we've usually already had kids before we get cancer. So even if we were to remove all of the carcinogens in the world, we wouldn't be able to completely stop mutation - meaning that, given long enough, our own DNA replication machinery will give us cancer. This does represent a very interesting drug target, though; if we were somehow able to reduce DNA Polymerase's error rate with pharmeceuticals, we'd be able to dramatically reduce the number of "background" replication errors and probably sharply decrease the risk of cancer. How we'd do that, though, is beyond my knoweldge.

Quote:

Thanks for the in depth answers by the way, they're really insightful.
You're welcome! I'm glad you're enjoying them.

Quote:

Originally Posted by Kanzler (Post 9286018)
To what extent do you collaborate with medical doctors in your work? Do you have a physician-scientist PI or perhaps have close ties with another lab that's more applied in nature? How often does your lab communicate with medical practitioners?

As far as I know, we don't have any collaborations going with medical doctors right now. The most that we do have is that we often recieve human samples from a nearby hospital, which are extremely valuable to us; it's much better to publish human-derived data than mouse-derived data, after all. It's quite difficult to collaborate with doctors in general because we approach our work from such different angles; we're focussed on molecular reasoning and mechanisms while doctors are more interested in drugs and overall outcomes for paitents. Medicine and medical research science are actually quite distantly detatched from each other, which is a shame since there are lots of benefits in combining the two; lots of the best PIs are physician-scientists, for sure, since they often have access to more data from humans and have better reasoning regarding the ultimate outcomes etc. from proposed treatments. Unfortunately though the relationship between scientists and medics remains very rocky for lots of reasons not only limited to what I just said above, so collaboration with medical doctors is difficult.

Quote:

Do you mind giving a bit more detail about the project you're working on? Like a mini-abstract or something.
I'm a little hesitant to provide an abstract since the project is still in its very early days and, while I'm certain that no-one on PokéCommunity just so happens to be looking to take the background from someone else's project, you can never be too careful - plus it's a principal thing that you don't just go publicly posting too much about your work, haha. What I'll say though is that, very broadly, we're investigating the role that EVs (which I mentioned in one of my earlier posts in this thread) have in the communication between cancer and stromal (i.e., "normal" tissue) cells, and how this communication favours the preparation of the bone as an environment for cancer metastasis - a sort of pre-metastatic niche, if you will. Since cancers secrete abundant amounts of EVs themselves in vivo along with secreted factors that are well-known to influence the cancer stroma, we believe that distant cancers such as those of the breast are able to prepare the bone microenvironment for their metastasis by means of these EVs, and that there's also the possibility that EVs derived from the pre-metastatic niche (the bone in this case) can mediate cross-talk between cells in this niche under the influence of cancer to prepare for metastasis. It's much more the first point that we're focussing on, though. I'll not give much more detail than this to keep things general; there are probably hundreds of groups working on the role of EVs in cancer progression and metastasis, and if I were to give any specific molecular details I fear that it'd divulge too much about the project. Sorry about that.

PastelPhoenix June 19th, 2016 7:52 AM

Don't actually have a question, just wanted to say I'm glad there's still a lot of work being done by people like you. I'm about 4 years remission from my own cancer (Nasopharyngeal), and although I don't think anyone ever really says their cancer treatment wasn't that bad, mine was actually a lot better than it could have been due to results from a recent study that apparently reevaluated the treatment for my specific cancer. So I guess that even though I think anonymous thanks over the internet are a little weird, and you mentioned you are in training... Thanks.

Leviathan June 22nd, 2016 12:55 AM

In school, the definition for cancer in my biology textbook was 'the uncontrolled growth of cells.' Now, for fear of sounding silly, what do cancer cells actually look like? Or, to be more specific, granted you've examined some samples, what have you seen cancer to ressemble with your own eyes. Do they in any way stand out from the structure of regular cells?

Nihilego June 22nd, 2016 1:29 PM

Quote:

Originally Posted by LeviathanX (Post 9294773)
In school, the definition for cancer in my biology textbook was 'the uncontrolled growth of cells.' Now, for fear of sounding silly, what do cancer cells actually look like? Or, to be more specific, granted you've examined some samples, what have you seen cancer to ressemble with your own eyes. Do they in any way stand out from the structure of regular cells?

Nah, you don't sound silly at all. I should point out though that what your textbooks probably meant by "growth" of cells likely referred to the uncontrolled growth and subsequent division of cancer cells - that means to say that usually, in terms of size, cancer cells are often slightly bigger than, but generally fairly comparible to, their healthy equivalents (although there are of course exceptions to this - for example, a range of common lung carcinomas which feature gigantic cells). However, the morphology of the cells (i.e., what they look like) is almost always changed in some way. This change in morphology varies a lot depending on which specific cancer we're talking about, though, and how far the cancer has progressed; highly metastatic cancer cells look quite different to their non-metastatic counterparts, for example. Here are some pictures of normal breast epithelial cells and two of their cancerous counterparts, which are examples of cells that we can use in the lab as models of breast cancer (a "cell line" is what we call cells which have been originally taken from some tissue and selected to be able to grow indefinitely in flasks in the lab assuming that they are handled properly; the majority of cell biology research is conducted on cell lines):

Spoiler: MCF-10A, a healthy breast epithelial cell line
http://www.lgcstandards-atcc.org/~/media/Attachments/2/1/8/0/CRL-10317%20Low%20High.ashx

These are healthy epithelial cells from the human mammary gland. They grow in ordered structures and pack together tightly as if trying to form a coherent tissue, as they would in an actual animal. When injected into mice, they do very little because they are not carcinogenic and do not cause neoplasia - the abnormal growth of new tissue.


Spoiler: MCF-7, a cancerous but relatively unaggressive breast epithelial cell line
http://www.lgcstandards-atcc.org/~/media/Attachments/0/E/E/2/1980.ashx

These cells are similar to those which I showed above, but are cancerous. You can probably immediately appreciate that, at low density, these cells are very spread-out and form large, flat structures. This immediate difference suggests that they are "searching" for other cells to grow alongside and indeed, when you look at the second panel, you can see that upon contacting each other these cells can start to form structures which vaguely resemble those formed by the above MCF-10A cells. The key difference, however, is how disordered the structure is; these cells have a very mixed morphology which resembles the sort of disorder that you'd expect to see in a cancerous tissue. This sort of growth would not be observed in normal tissue and indeed, in mice, after a (sometimes very long) while these cells do start to form breast tumours. However they are not particularly aggressive - they grow slowly and do not invade other tissues much. Compare that to these next ones--


Spoiler: MDA-MB-231, a highly aggressive human breast cancer cell line
http://www.lgcstandards-atcc.org/~/media/Attachments/5/C/3/0/25935.ashx

These are actually the same original type of cell as the MCF-10A above, but you can see instantly that they look extremely dissimilar. These cells are what's described as "spindle-shaped"; that is, they have several "pointy" edges which they lead with when migrating. This is because they are attempting to invade foreign tissues - these are extremely aggressive cells which metastasise rapidly in mice, partly due to their morphology being suited to moving through tissues. You might notice also that they do not form coherent tissues like MCF-10A and, to an extent, MCF-7; they rapidly grow over and compete with each other instead of forming a single mass of tissue. This is reminiscent of highly advanced cancers which have virtually no discernible order or structure to them, instead appearing simply as a messy mass of cells.


So really it depends a lot on which cell we're talking about and how aggressive it is; but almost always, cancer cells grow either inconsistent or completely incoherent tissues and often display features suggesting that they are more migratory than normal cells, and in some cases more invasive.

If you're asking more about what a whole tumour looks like, while I'll spare your eyes by not posting the images here, in a word: messy. They're usually large growths with few clear defining features. They have a complex network of disordered blood vessels running through them which feed nutrients to the tumour; these vessels themselves grow because cancer cells can instruct the surrounding tissue to grow them themselves. Sometimes in particularly large tumours you can see smaller tumour-like structures or discrete sheets of cells on the original mass, indicating sub-populations of cancer cells which are genetically different to those in the main body. They can be pretty complex structures when quite advanced.

Hope this answers your question!


All times are GMT -8. The time now is 11:23 PM.


Like our Facebook Page Follow us on Twitter © 2002 - 2018 The PokéCommunity™, pokecommunity.com.
Pokémon characters and images belong to The Pokémon Company International and Nintendo. This website is in no way affiliated with or endorsed by Nintendo, Creatures, GAMEFREAK, The Pokémon Company or The Pokémon Company International. We just love Pokémon.
All forum styles, their images (unless noted otherwise) and site designs are © 2002 - 2016 The PokéCommunity / PokéCommunity.com.
PokéCommunity™ is a trademark of The PokéCommunity. All rights reserved. Sponsor advertisements do not imply our endorsement of that product or service. User generated content remains the property of its creator.

Acknowledgements
Use of PokéCommunity Assets
vB Optimise by DragonByte Technologies Ltd © 2023.