Summary.lyx

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Summary
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When starting my doctorate, even though I had a plan of research and experiments
 written out and arranged in my head, I could not expect the final form
 my doctorate would take.
 I expected my doctorate to combine different fields of science, but I could
 not expect my doctorate to be, so interdisciplinary.
 I could not expect, the pandemic that started in 2019, and that in 2020
 it would lock me in complete isolation for two weeks.
 I tried to make the most of the time in quarantine by conducting 
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 research, despite the 
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 research that had already begun.
 
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może tu coś więcej?
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I think the great advantage of presenting one's PhD as a set of publications
 linked by a common theme is that one tends to present things that more
 or less came out well, things we are satisfied with—we do not have to go
 back to things that did not come out, didn't have a chance to come out,
 things that demotivated us on a daily basis and kept us up at night.
 Of course, these things also happened during my doctorate, and I think
 it's important for other, younger, researchers to realize that a lot of
 the lines of research I undertook did not result in pushing the state of
 science forward, or an article—what was collected and presented in this
 thesis is the essence of hard work, but also luck.
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This PhD has been the investigation of properties of 
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, particularly 
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.
 I do believe that contributions in the form of the articles presented here
 are of importance at a basic research level, but they also provide a foundation
 on which to build applied research.
 Understanding the assemblies formed by 
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 may eventually lead to the creation of a model that could predict the interprot
ein metal binding from the structure or sequence of a protein.
 Correspondingly, filling the missing pieces of the metal–protein interaction
 in the protein–protein interaction puzzle can offer insight into the metal-depe
ndent regulation of the interaction, as well as help to identify novel interacti
ons that were missing from the picture due to the metal dependence.
 From a medical perspective, understanding 
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 can give insight into diseases associated with abnormal metal-induced aggregati
on (e.g., crystallins in the eye) 
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key "Ramirez-Bello2022"
literal "true"

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, and how mismetallation of those sites may cause various diseases.
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I am glad that all the publications presented here are available in open
 access, this allows other researchers to freely read and use the information
 meticulously prepared by us.
 This is truly important in the case of 
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LatexCommand citetitle
key "Kocyla2021"
literal "true"

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 where we present the curated data set of the physiological 
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.
 The 
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part of my doctorate focused on the 
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 protein, as the data presenting the 
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 properties are still unpublished as of March 6, 2023, the 
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 makes a great foundation for the discussion of the properties of the 
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 protein.
 The study lays out the basis of the long-range allostery between the zinc
 hook and the rest of the protein.
 To my knowledge, the described stabilization of the Zn(
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2
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 is the first example of complex stabilization over such a long distance.
 The description of the link between the 
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 damage response with the biology of Zn(II) ions and signal transduction
 pathways can be a great step in the apprehension of the metal dynamics
 in cancer cells.
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może tu coś jeszcze?
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To last two articles presented in the thesis show how detrimental is for
 the zinc-binding sites the mismetallation by heavy metal ions.
 Those articles, together with 
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 are the first articles addressing the issue of mismetallation of interprotein
 metal binding sites.
 Our studies provide an explanation of a potential genotoxic mechanism of
 mismetallation of the zinc hook.
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Though the article describing InterMetalDB was published in a journal with
 a lower 
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 the article describing physiological 
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, 
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 I think that this is a much more fundamental contribution in this field.
 Most of the previous surveys regarding the existence of metal ions in 
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 structures gather the data as a spreadsheet that is usually available after
 an exchange of emails, the same goes for the algorithms that were used
 to select the data.
 Even when the data is publicly available, the data is created only once
 and is no longer updated (as in the case of 
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, and similar studies).
 InterMetalDB is different—data presented in InterMetalDB is available after
 a few mouse clicks via the web interface, moreover, the resource is constantly
 updated, without any human involvement.
 The resource will be updated as long as the service is maintained, unfortunatel
y, nobody, especially in the academy, can guarantee that the service will
 be maintained forever, where the service does not generate any revenue.
 Not surprisingly, even the services that were published last year are no
 longer available, and the URLs point to 
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404 Not Found
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.
 With that thought in mind, I have envisioned InterMetalDB to be an open
 
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 project—freely available and reproducible.
 Any function, any component of InterMetalDB can be used by anyone, researcher
 or not, one only has to click 
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copy
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, or 
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fork
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 repository on GitHub, instead of wasting time to recreate the whole service
 from the source article.
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I believe that conducting research in line with open science principles
 (
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, providing free access to publications, data, software, and 
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) is the next step in the evolution of scientific knowledge dissemination
 in the age of the Internet, as it was with 17th-century advent of scientific
 journal during the Scientific Revolution.
 Already some principles of open science make the publication presented
 in the thesis available to the reader without the need to pay for the informati
on, InterMetalDB and its resources are pushed the furthest in accordance
 with the principles of open science, which makes the InterMetalDB easily
 reproducible even after the ceasing of hosting.
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